摘要
2-DG抗痫作用的评价
目的：探讨2-DG抗痫作用的疗效。
方法：6-8周成年雄性C57BL/6小鼠进行随机分配为对照组、致痫组、2-DG干预组,建立匹罗卡品致痫模型。对不同组行为学的变化进行监测,观察其自发性痫性发作的癫痫潜伏期、癫痫评分、痫性发作持续时间,同时观察不同组脑电图的变化。
结果：
1.对不同组(对照组、致痫组、2-DG干预组)行为学监测显示：与对照组相比,匹罗卡品致痫后,致痫组、2-DG干预组41.5%的C57BL/6小鼠存在自发性痫性发作。相对于致痫组,中、高剂量2-DG干预组小鼠潜伏期增加,癫痫发作评分、痫性发作持续时间降低(癫痫潜伏期：15±4分钟VS35±4、33±5分钟；癫痫评分为5.1±0.5VS3.9±0.4、3.8±0.5；痫性发作持续时间为122±7分钟VS35±6分钟、42±7分钟),而且有统计学意义。
2.对不同组(对照组、致痫组、2-DG干预组)脑电图监测显示：对照组脑电图是以α、β波为主且波幅较小；匹罗卡品致痫模型组可见大量的尖波、棘波和尖慢波：2-DG干预组脑电图是也主要是以α、β波为主且波幅较小。
结论：
2-DG在匹罗卡品癫痫模型中具有抗痫作用。
2-DG上调KATP亚基Kir6.1、Kir6.2发挥抗痫作用
目的：研究糖酵解抑制剂2-DG对ATP依赖性钾离子通道亚基Kir6.1、 Kir6.2mRNA和蛋白表达的影响与抗痫作用的关系。
方法：
1.6-8周成年雄性C57BL/6小鼠进行随机分配为对照组、致痫组、2-DG干预组,建立匹罗卡品致痫小鼠模型。将造模成功的小鼠(致痫组,2-DG干预组)在癫痫持续状态(SE)后4小时、1天、7天、30天、60天和正常生理盐水对照组(各组n=4-6)的海马组织应用Real-time PCR方法检测使用糖酵解抑制剂2-DG前后各组小鼠海马组织中ATP敏感性钾通道亚基Kir6.1、Kir6.2mRNA的变化。
2.将造模成功的小鼠(致痫组、2-DG干预组)在癫痫持续状态(SE)后4小时、1天、7天、30天、60天和对照组(各组n=4-6)的海马组织应用western-blot方法检测糖酵解抑制剂2-DG前后各组小鼠海马组织中ATP敏感性钾通道亚基Kir6.1、Kir6.2mRNA蛋白的变化。
结果：
1.相对于对照组,在第1、7、30天致痫组小鼠海马组织Kir6.1和Kir6.2mRNAs上调,而且有统计学意义；相对于致痫组,在第1、7、30天中、高剂量2-DG干预组海马组织Kir6.1和Kir6.2mRNAs上调,而且有统计学意义。在其它时间点差异不明显。
2.相对于对照组,在第1和30天致痫组小鼠海马组织Kir6.1蛋白上调,而且有统计学意义；在第1、7天致痫组小鼠海马组织Kir6.2蛋白上调,而且有统计学意义；相对于致痫组,在第1天中、高剂量2-DG干预组海马组织Kir6.1蛋白上调,而且有统计学意义。在第1、7、30天中、高剂量2-DG干预组海马组织Kir6.2蛋白上调,而且有统计学意义。在其它时间点差异不明显。
结论：
糖酵解抑制剂2脱氧葡萄糖上调KATP亚基Kir6.1、Kir6.2mRNA和蛋白表达发挥抗痫作用。
2-DG经KATP通道抗痫作用机制体外实验研究
目的：探讨2-DG经KATP通道抗痫作用的机制
方法：
1.在体外海马脑片CA3区,给予10uM荷包牡丹碱、7.5mM高钾模拟痫性发作,诱发动作电位频率增加,应用盲法膜片钳技术监测使用10mM2-DG前后神经元细胞动作电位频率的变化。
2.在体外海马脑片CA3上,高频电刺激诱发LTPGlu模拟致痫模型,记录给予2-DG后海马脑片CA3区神经元LTPGlu(谷氨酸介导突触传递的长时程增强)的变化；给予KATP通道激活剂Diazoxide (300nM),LTPGlu的变化以及在KATP通道抑制剂Gliben (20uM)预处理后给予10mM2DG后LTPGlu的变化。
结果：
1.在体外海马脑片CA3区上,10mM2-DG降低荷包牡丹碱和高钾致痫模型的动作电位频率。
2.在体外海马脑片CA3区上,高频电刺激诱发LTPGlu模拟致痫模型,10mM2-DG阻挡高频电刺激诱发LTPGlu。
3. Kir6.2通道激动剂Diazoxide (300nM)阻挡高频电刺激诱发海马CA3区神经元LTPGlu, Kir6.2通道阻断剂Gliben (20uM)拮抗2-DG (10mM)阻挡高频电刺激诱发海马CA3区神经元LTPGlu作用。
结论：
2-DG在体外脑片致痫模型上具有抗痫作用,其机制是经KATP通道的激活而发挥抗痫作用。
2-DG抗痫作用的信号通路研究
目的：研究糖酵解抑制剂2-DG抗痫作用的信号通路。
方法：
1.在体内匹罗卡品致痫模型上,采用Elisa技术记录使用糖酵解抑制剂2-DG前后静脉血中DAG的变化。
2.在体外海马脑片上,高频电刺激诱发LTPGlu模拟致痫模型,给予PKC激动剂phorbol(PMA)预处理后,应用盲法膜片钳技术记录给予2-DG前后LTPGlu的变化。
结果：
1.在体内匹罗卡品致痫模型中,相对于对照组,在第1天致痫组小鼠静脉血DAG上调,而且有统计学意义(p<0.05)；在第7、30、60天致痫组小鼠静脉DAG下调,其中第7、30天致痫组小鼠静脉DAG下调有统计学意义(p<0.05)。
2.相对于致痫组,在第1天中、高剂量2-DG干预组小鼠静脉DAG上调,而且有统计学意义(p<0.01)；在第7、30、60天中、高剂量2-DG干预组小鼠静脉DAG下调,其中第7、30天致痫组小鼠静脉DAG下调有统计学意义(p<0.05),在其它时间点差异不明显。
3.在体外海马脑片上,PKC激动齐(?)phorbol(500nM)拮抗2-DG(10mM)阻挡高频电刺激诱发海马CA3区神经元LTPGlu作用
结论：
DAG的下降与2-DG的抗痫作用有关；PKC激动剂能抑制2-DG的抗痫作用。
Evaluation of the efficacy of antiepileptic effect of2-DG
Objective:Explore the efficacy of antiepileptic effect of2-DG
Methods:C57BL/6adult mice of6-8weeks were divided randomly into controls,seizure group and2-DG control group, and establish the seizure model of mice induced by pilocarpine. Observe the behavioral changes in different groups. Observe the latent period of seizure、score for seizure and time of duration in seizure group and2-DG intervention group. Meanwhile. Observe the EEG changes in different groups.
Results:
1.Different group (Control group, seizure group,2-DG intervention group) behavioral monitoring:Compared with Control group,41.5%of seizure group and2-DG intervention group mice have spontaneous seizures induced by pilocarpine. Compared with seizure group, the latent period of seizure prolonged and score for seizure and time duration of seizure shortened in middle and high dose2-DG control groups with statistical significance (the latent period of seizure:15±4min VS35±4、33±5min; score for seizure5.1±0.5VS3.9±0.4、3.8±0.5; time duration of seizure122±7minVS35±6、42±7min)
2.Different group (Control group, seizure group,2-DG intervention group) EEG monitoring:the result of normal control group EEG is mainly alpha, beta-wave. and the amplitude is relatively lower. the result of seizure group is a large number of sharp、spikes and sharp slow-wave;And the result of2-DG intervention group EEG is mainly alpha, beta-wave. and the amplitude is relatively lower.
Conclusion:
In pilocarpine epilepsy model.2-DG play antiepileptic effect. The antiepileptic effect of2-Deoxy-D-Glucose is mediated by up-regulation of
ATP-sensitive potassium channel Subunits Kir6.1and Kir6.2
Objective:Investigate the relationship between the antiepileptic effect of glycolysis inhibitors2-deoxyglucose and expressions of Kir6.1and Kir6.2subunits mRNA and protein of ATP-sensitive potassium channel (KATP channel).
Methods:
1. C57BL/6adult mice of6-8weeks were divided randomly into controls, seizure group and2-DG control group, and establish the seizure model of mice induced by pilocarpine.Apply Real-time PCR to detect expressions of Kir6.1and Kir6.2mRNA of ATP-sensitive potassium channel in vivo before and after treatment of glycolysis inhibitors2-DG in4hours,1day,7days,30days,60days of successfully modeling mice in seizure group and2-DG experiment group, and compare with the controls(n=10for each group).
2. Apply western-blot to to detect change of Kir6.1and Kir6.2protein in vivo before and after treatment of glycolysis inhibitors2-DG in4hours,1day,7days,30days,60days of seizure group,2-DG experiment group and controls.
Results:
1. Compared with control group, Kir6.1and Kir6.2mRNA were up-regulated in hippocamal tissue of1、7、30days seizure groups with statistical significance; Compared with seizure group, Kir6.1and Kir6.2mRNA were up-regulated in hippocamal tissue in1、7、30days high does2-DG experiment group significantly, and insignificantly in other time points.
2.Compared with control group, Kir6.1protein up-regulated in hippocamal tissue of1and30days seizure groups significantly; Kir6.2protein up-regulated in1and7days seizure groups significantly; Compared with seizure group, Kir6.1protein up-regulated in the first day of high does2-DG group significantly; in1,7,30days high does2-DG groups, Kir6.2protein up-regulated significantly, and insignificantly in other time points.
Conclusion:
Glycolysis inhibitors2-deoxy glucose plays antiepileptic effect through mediating up-regulation of ATP-sensitive potassium channel subunits Kir6.1and Kir6.2.
The study of2-DG plays antiepileptic effect through mediating the ATP-sensitive potassium channel in vitro
Objective:Explore the mechanism of2-DG play antiepileptic effect through mediating ATP-sensitive potassium channel.
Methods:
1.Give lOuM bicuculine,7.5mM high potassium stimulate seizure and induce the increase of the frequency of action potential in vitro CA3region of hippocamal slice. apply blinded clamp patch to record change of neural action potential frequency before and after intervention of10mM2-DG.
2. establish high frequency stimulation induce long-term potentiation (LTPGlu) which simulate model of epilepsy in vitro CA3region of hippocamal slice, apply blinded clamp patch to record change of glutamic acid mediated LTPGlu of synaptic transmission before and after intervention of2-DG、the activator of KATP Diazoxide (300nM) and inhibitor of KATP Gliben (20uM)
Results:
1.2-DG lowers neural discharge frequency in CA3region neurons of hippocamal slice in bicuculine and high potassium epilepsy models.
2.2-DG blockades LTPGlu in high frequency stimulation epilepsy model in CA3region neurons of hippocamal slice
3. Kir6.2channel activator Diazoxide lowers LTPGlu in CA3region neurons of hippocamal slice in high frequency stimulation epilepsy model, while Kir6.2channel inhibitor Gliben presents inhibition in the antiepileptic effect of2-DG
Conclusion:
2-DG exhibits antiepileptic effect in vitro brain slices epileptogenic models. And the mechanism is2-DG play antiepileptic effect through mediating the activation of ATP-sensitive potassium channel.
The study of the signaling pathway of antiepileptic effect of2-DG
Objective：Study signaling pathway of antiepileptic effect of2-DG.
Methods:
1. In vivo pilocarpine epilepsy model, apply Elisa to detect venous blood DAG before and after use of2-DG.
2.Establish high frequency stimulation models in vitro hippocamal slice, apply blinded clamp patch to record change of LTPGlu pretreated by2-DG after intervention of PKC activator phorbol(PMA).
Results:
1. In vivo pilocarpine epilepsy model, compared with control group, venous blood DAG of1day seizure group up-regulated significantly (p<0.05); DAG in7,30and60days seizure groups down-regulates, significantly in7and30days groups (p<0.05).
2. Compared with seizure group, DAG of1day high-does2-DG experiment group up-regulated significantly (p<0.05), and down-regulates in7,30and60days high-does2-DG experiment groups, significantly in7and30days groups (p<0.05) and insignificantly in other time points.
3. In vitro hippocamal slice, PKC activator phorbol (500nM) shows to inhibit the2-DG effect of lowering neuron LTPGlu.
Conclusion:
There is a relationship between the reduce of DAG and the anti-epileptic effect of2-DG. PKC agonists can inhibit the anti-epileptic effect of2-DG's.
引文
[1]Scharfman HE. The neurobiology of epilepsy [J]. Curr Neurol Neurosci Rep, 2007,7(4):348-354.
[2]Berg AT. Defining intractable epilepsy.Adv Neurol.2006,97:5-10.
[3]Wasterlain CG, Thompson KW, Suchomelova L,et al. Brain energy metabolism during experimental neonatal seizures.Neurochem Res.2010,35(12):2193-2198.
[4]Vining EP. Clinical efficacy of the ketogenic diet.Epilepsy Res.1999,37(3):181-190.
[5]Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet.Epilepsia. 2007,48(1):43-58.
[6]Huttenlocher PR. Ketonemia and seizures:metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res.1976,10(5):536-540.
[7]Gasior M, Yankura J, Hartman AL, et al. Anticonvulsant and proconvulsant actions of 2-deoxy-D-glucose. Epilepsia.2010,51(8):1385-1394.
[8]Stringer JL, Xu K. Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphate. Epilepsia.2008,49 Suppl 8:101-103.
[9]Stafstrom CE, Ockuly JC, Murphree L, et al. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol.2009,65(4):435-447.
[10]Stafstrom CE, Roopra A, Sutula TP. Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia.2008,49 Suppl 8:97-100.
[11]Garriga-Canut M, Schoenike B, Qazi R, et al.2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci.2006,9(11):1382-1387.
[12]Gasior M, Yankura J, Hartman AL, et al. Anticonvulsant and proconvulsant actions of 2-deoxy-D-glucose. Epilepsia.2010,51(8):1385-1394.
[13]Huang YZ, McNamara JO. Inhibiting glycolysis to reduce seizures:how it might work. Nat Neurosci.2006,9(11):1351-1352.
[14]Seino S, Miki T. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol.2003,81(2):133-176.
[15]Dubinsky WP,Mayorga-Wark O,Schultz SGColocalization of glycolytic enzyme activity and KATP channels in basolateral membrane of Necturus enterocytes.Am J Physiol.1998,275:C1653-1659.
[16]Mercer RW, Dunham PB. Membrane-bound ATP fuels the Na/K pump. Studies on membrane-bound glycolytic enzymes on inside-out vesicles from human red cell membranes. J Gen Physiol.1981,78 (5):547-568.
[17]Ma W, Berg J, Yellen G. Ketogenic diet metabolites reduce firing in central neurons by opening K (ATP) channels.J Neurosci.2007,27 (14):3618-3625.
[18]Binder DK, Routbort MJ, McNamara JO. Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus. J Neurosci.1999,19 (11):4616-4626.
[19]Rivera C, Voipio J, Thomas-Crusells J, et al. Mechanism of activity-down regulation of the neuron-specific K-Cl cotransporter KCC2.J Neurosci.2004, 24(19):4683-4691.
[20]He XP, Minichiello L, Klein R, et al. Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus. J Neurosci.2002,22 (17):7502-7508.
[21]He XP,Pan E,Sciarretta C,et al. Disruption of trkB-mediated PLCy signaling inhibits limbic epileptogenesis. J Neurosci.2010,30 (18):6188-6196.
[22]Niimura M, Moussa R, Bissoon N, et al. Changes in phosphorylation of the NMDA receptor in the rat hippocampus induced by status epilepticus.J Neurochem. 2005,92(6):1377-1385.
[23]Silva AP,Lourenco J,Xapelli S,et al.Protein kinase C activity blocks neuropeptide Y-mediated inhibition of glutamate release and contributes to excitability of the hippocampus in status epilepticus.FASEB J.2007,21(3):671-681.
[24]Fuortes MG, Faria LC, Merlin LR. Impact of protein kinase C activation on epileptiform activity in the hippocampal slice.Epilepsy Res.2008,82(1):38-45.
[25]Aziz Q, Thomas AM, Khambra T, et al. Regulation of the ATP-sensitive Potassium Channel Subunit, Kir6.2, by a Ca2+-dependent Protein Kinase C.J Biol Chem.2012,287(9):6196-6207.
[26]Shi Y, Cui N, Shi W, et al. A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the vascular KATP channel inhibition by protein kinase C. J Biol Chem.2008,283(5):2488-2494.
[27]Park WS, Ko EA, Han J, et al. Endothelin-1 acts via protein kinase C to block KATP channels in rabbit coronary and pulmonary arterial smooth muscle cells. J Cardiovasc Pharmacol.2005,45(2):99-108.
[28]Stringer JL, Xu K. Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphate.Epilepsia.2008,49 Suppl 8:101-103.
[29]Lian XY, Stringer JL.Inhibition of aconitase in astrocytes increases the sensitivity to chemical convulsants. Epilepsy Res.2004,60(l):41-52.
[30]Bough KJ, Gudi K, Han FT,et al. An anticonvulsant profile of the ketogenic diet in the rat.Epilepsy Res.2002,50(3):313-325.
[31]Avanzi RD, Cavarsan CF, Santos JG, et al. Basal dendrites are present in newly born dentate granule cells of young but not aged pilocarpine-treated chronic epileptic rats. Neuroscience.2010,27:687-691.
[32]Covolan L, Mello LE. Assessment of the progressive nature of cell damage in the pilocarpine model of epilepsy. Braz J Med Biol Res.2006,39:915-924.
[33]Snead OC.y-Hydroxybutyrate model of generalized absence seizure:further characterization and comparison with other absence model. Epilepsia.1988,29(2):361.
[34]王晓鹏,王维平.化学药物点燃动物癫痫模型的研究进展.脑与神经疾病杂志.2006,14(6)：475-478.
[35]Zita Q Erika G,Edit H,et al.Involement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo.Epilepsia.2003,44(12): 1596-1600.
[36]Tange S, Scherer MN, Graeb C, et al.The antineoplastic drug Paclitaxel has immunosuppressive properties that can effectively promote allograft survival in a rat heart transplant model.Transplantation.2002,73(2):216-223.
[37]Klioueva IA, Van Luijtelaar ELJM, Chepurnova NE, et al. PTZ-induced seizures in rats:effects of age and strain.PHYSIOL BEHAV.2001,72(3):421-426.
[38]Sperk G. Kainic acid seizures in the rat.Prog Neurobiol.1994,42(1):1-32
[39]Le Duigou C, Wittner L, Danglot L, et al. Effects of focal injection of kainic acid into the mouse hippocampus in vitro and ex vivo. J Physiol.2005,569(Pt 3):833-847.
[40]Savolainen KM, Hirvonen MR.Second messengers in cholinergic-induced convulsions and neuronal injury. Toxicol Lett.1992,64-65:437-445.
[41]Clifford DB,Olney JW, Maniotis A,et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures.Neuroscience.1987,23:953-968.
[42]Smolders I, Khan GM,Manil J, et al. NMDA receptor-mediated pilocarpine-induced seizures:Characterization in freely moving rats by microdialysis. Br J Pharmacol.1997,121:1171-1179.
[43]Nagao T,Alonso A, Avoli M. Epileptiform activity induced by pilocarpine in the rat hippocampal-entorhinal slice preparation.Neuroscience.1996,72:399-408.
[44]Kapur J,Macdonald RL.Rapid seizure-induced reduction of benzodiazepine and zn2+ sensitivity of hippocampal dentate granule cell gabaa receptors. J Neurosci.1997,17:7532-7540.
[45]Cao X, Xiao H, Zhang Y, et al.1,5-Dicaffeoylquinic acid-mediated glutathione synthesis through activation of Nrf2 protects against OGD/reperfusion-induced oxidative stress in astrocytes. Brain Res. 2010,1347:142-148.
[46]Zhou M, Tanaka O, Suzuki M, et al. Localization of pore-forming subunit of the ATP-sensitive K(+)-channel, Kir6.2, in rat brain neurons and glial cells. Brain Res Mol Brain Res.2002,101(1-2):23-32.
[47]Liss B, Bruns R, Roeper J. Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. EMBO J.1999,18(4):833-846.
[48]Rodrigo GC, Standen NB, ATP-sensitive potassium channels. Curr Pharm Des. 2005,11(15):1915-1940.
[49]Yamada K, Ji JJ, Yuan H, et al. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science.2001,292(5521):1543-1546.
[50]Soundarapandian MM, Wu D, Zhong X, et al. Expression of functional Kir6.1 channels regulates glutamate release at CA3 synapses in generation of epileptic form of seizures. J Neurochem.2007,103(5):1982-1988.
[51]Yellen G. Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet.Epilepsia.2008,49 Suppl 8:80-82.
[52]Katsumori H, Ito Y, Higashida H, et al. Anti- and proconvulsive actions of levcromakalim, an opener of ATP-sensitive K+ channel, in the model of hippocampus -generating partial seizures in rats. Eur J Pharmacol.1996,311(1):37-44.
[53]Gandolfo G, Romettino S, Gottesmann C, et al. K+ channel openers decrease seizures in genetically epileptic rats. Eur J Pharmacol.1989,167(1):181-183.
[54]Jiang KW, Gao F, Shui QX, et al. Effect of diazoxide on regulation of vesicular and plasma membrane GAB A transporter genes and proteins in hippocampus of rats subjected to picrotoxin-induced kindling. Neurosci Res.2004,50(3):319-329.
[55]Ghasemi M, Shafaroodi H, Karimollah AR, et al. ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole -induced seizure threshold in diabetic mice. Seizure.2010,19(1):53-58.
[56]Jiang K, Shui Q, Xia Z, Yu Z. Changes in the gene and protein expression of K(ATP) channel subunits in the hippocampus of rats subjected to picrotoxin-induced kindling. Brain Res Mol Brain Res.2004,128:83-89
[57]Jiang K, Yu Z, Shui Q. The pattern of ATP-sensitive K+ channel subunits, Kir6.2 and SUR1 mRNA expressions in DG region is different from those in CA1-3 regions of chronic epilepsy induced by picrotoxin in rats. Neuropathology.2007,27: 531-538
[58]Palizvan MR, Fathollahi Y, Semnanian S, Hajezadeh S, Mirnajafizadh J. Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus. Brain Res.2001,898:82-90
[59]Curia G, Longo D, Biagini G, Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods.2008,172:143-157
[60]Landfield PW. Aging-related increase in hippocampal calcium channels.Life Sci.1996,59(5-6):399-404.
[61]Gloveli T, Schmitz D, Heinemann U. Interaction between superficial layers of the entorhinal cortex and the hippocampus in normal and epileptic temporal lobe.Epilepsy Res.1998,32(1-2):183-193.
[62]Grassi S, Pettorossi VE. Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.Prog Neurobiol.2001,64(6):527-553.
[63]Jiruska P, Csicsvari J, Powell AD, et al. High-frequency network activity, global increase in neuronal activity, and synchrony expansion precede epileptic seizures in vitro. J Neurosci.2010, 30(16):5690-5701.
[64]Neher E, Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres.Nature.1976.260(5554):799-802.
[65]Edwards FA, Konnerth A, Sakmann B, et al. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system.Pflugers Arch.1989,414(5):600-612.
[66]Blanton MG, Lo Turco JJ, Kriegstein AR.Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J Neurosci Methods.1989, 30(3):203-210.
[67]Woodruff TM, Thundyil J, Tang SC,et al.Pathophysiology, treatment, and animal and cellular models of human ischemic stroke.Mol Neurodegener.2011, 6(1):11.
[68]Ashcroft FM. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci.1988,11:97-118.
[69]Tucker SJ, Gribble FM, Proks P, Molecular determinants of KATP channel inhibition by ATP.EMBO J.1998,17(12):3290-3296.
[70]Kristiansen SB, Henning O, Kharbanda RK, et al. Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol.2005,288(3):H1252-1256.
[71]Blandini F, Nappi G, Tassorelli C, Martignoni E. Functional changes of the basal ganglia circuitry in Parkinson's disease. Prog Neurobiol.2000,62(1):63-88.
[72]Kimura S, Zhang GX, Nishiyama A, et al. Role of NAD(P)H oxidase- and mitochondria-derived reactive oxygen species in cardioprotection of ischemic reperfusion injury by angiotensin II. Hypertension.2005,45(5):860-866.
[73]Miki T, Liss B, Minami K, ATP-sensitive K+channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci. 2001,4(5):507-512.
[74]Nugent FS, Penick EC, Kauer JA. Opioids block long-term potentiation of inhibitory synapses.Nature.2007,446(7139):1086-1090.
[75]Rebecchi MJ, Pentyala SN. Structure, function, and control of phosphoinositide-specific phospholipase C.Physiol Rev.2000,80(4):1291-1335.
[76]Fukami K. Structure, regulation, and function of phospholipase C isozymes.J Biochem.2002,131 (3):293-299.
[77]Offermanns S, Toombs CF, Hu YH, et al.Defective platelet activation in G alpha(q)-deficient mice.Nature.1997,389(6647):183-186.
[78]Carpenter G, Ji Qs.Phospholipase C-gamma as a signal-transducing element. Exp Cell Res.1999,253(1):15-24.
[79]Essen LO, Perisic O, Cheung R, et al.Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.Nature.1996,380(6575):595-602.
[80]Ferguson KM, Lemmon MA, Schlessinger J, et al.Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain.Cell.1995,83(6):1037-46.
[81]Noh DY, Shin SH, Rhee SGPhosphoinositide-specific phospholipase C and mitogenic signaling. Biochim Biophys Acta.1995,1242(2):99-113.
[82]Rhee SG, Choi KD.Regulation of inositol phospholipid-specific phospholipase C isozymes.J Biol Chem.1992,267(18):12393-12396.
[83]Ye K, Aghdasi B, Luo HR, et al. Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE.Nature. 2002,415(6871):541-544.
[84]ExtonJH. Signaling through PhosPhatidyleholine breakdown. JBiol Chem. 1990,265(1):1-4.
[85]Nishizuka Y, Takai Y, Kishimoto A, et al.A role of calcium in the activation of a new protein kinase system. Adv Cyclic Nucleotide Res.1978,9:209-220.
[86]Adams JM, Cory S.The Bcl-2 protein family:arbiters of cell survival. Science. 1998,281(5381):1322-6.
[87]Azzi A, Boscoboinik D, Hensey C.The protein kinase C family. Eur J Biochem. 1992,208(3):547-557.
[88]Shi Y, Cui N, Shi W, et al. A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the vascular KATP channel inhibition by protein kinase C. J Biol Chem.2008,283(5):2488-2494.
[89]Di Paolo G, De Camilli P.Phosphoinositides in cell regulation and membrane dynamics.Nature.2006,443(7112):651-657.
[90]Krauss M, Haucke V. Phosphoinositide-metabolizing enzymes at the interface between membrane traffic and cell signalling. EMBO Rep.2007,8(3):241-246.
[91]Quinn KV, Cui Y, Giblin JP, et al. Do anionic phospholipids serve as cofactors or second messengers for the regulation of activity of cloned ATP-sensitive K+ channels? Circ Res.2003,93(7):646-655.
[92]Zeng WZ, Li XJ, Hilgemann DW,et al.Protein kinase C inhibits ROMK1 channel activity via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. J Biol Chem.2003,278(19):16852-16856.
[93]Nasuhoglu C, Feng S, Mao Y, et al. Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions.Am J Physiol Cell Physiol.2002,283(1):C223-234.
[94]Newton AC.Protein kinase C:structure, function, and regulation.J Biol Chem. 1995,270(48):28495-28498.
[1]Scharfman HE. The neurobiology of epilepsy [J]. Curr Neurol Neurosci Rep, 2007,7(4):348-354.
[2]Birbeck G, Chomba E, Atadzhanov M, et al. The social and economic impact of epilepsy in Zambia:a cross-sectional study. Lancet Neurol.2007,6(1):39-44.
[3]Wasterlain CG, Fujikawa DG, Penix L, et al. Pathophysiological mechanisms of brain damage from status epilepticus.Epilepsia.1993,4 Suppl 1:S37-53.
[4]Williamson A, Patrylo PR, Pan J,et al. Correlations between granule cell physiology and bioenergetics in human temporal lobe epilepsy.Brain.2005,128(Pt 5):1199-1208.
[5]Osorio I, Frei MG, Sornette D,et al. Epileptic seizures:Quakes of the brain? Phys Rev E Stat Nonlin Soft Matter Phys.2010,82(2 Pt 1):021919.
[6]Federico P, Abbott DF, Briellmann RS, et al. Functional MRI of the pre-ictal state. Brain.2005,128(Pt 8):1811-1817.
[7]Wasterlain CG, Thompson KW, Suchomelova L, et al. Brain energy metabolism during experimental neonatal seizures.Neurochem Res. 2010,35(12):2193-2198.
[8]Kossoff EH, McGrogan JR. Worldwide use of the ketogenic diet.Epilepsia. 2005,46(2):280-289.
[9]Huttenlocher PR.Ketonemia and seizures:metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy.Pediatr Res.1976,10(5):536-540.
[10]Semenza GL. Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J.2007,405(1):1-9
[11]Zancan P, Marinho-Carvalho MM, Faber-Barata J, et al. ATP and fructose-2, 6-bisphosphate regulate skeletal muscle 6-phosphofructo-l-kinase by altering its quaternary structure. IUBMB Life.2008,60(8):526-533.
[12]Uyeda K. Phosphofructokinase. Adv Enzymol Relat Areas Mol Biol. 1979,48:193-244.
[13]Wasterlain CG, Fujikawa DG, Penix L, et al. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia.1993,34 Suppl 1:37-53.
[14]Wasterlain CG, Thompson KW, Suchomelova L, et al. Brain energy metabolism during experimental neonatal seizures. Neurochem Res.2010,35(12): 2193-2198.
[15]Folbergrova J, Jesina P, Drahota Z, et al. Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures. Exp Neurol.2007,204(2):597-609.
[16]Acharya MM, Katyare SS. Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain. Exp Neurol. 2005,192(1):79-88.
[17]Waldbaum S, Patel M. Mitochondria, oxidative stress and temporal lobe epilepsy. Epilepsy Res.2010,88(1):23-45.
[18]Sacktor B, Wilson JE, Tiekert CG. Regulation of glycolysis in brain, in situ, during convulsions. J Biol Chem.1966,241(21):5071-5075.
[19]Neppl R, Nguyen CM, Bowen W, et al. In vivo detection of postictal perturbations of cerebral metabolism by use of proton MR spectroscopy:preliminary results in a canine model of prolonged generalized seizures. AJNR Am J Neuroradiol. 2001,22(10):1933-1943.
[20]Slais K, Vorisek I, Zoremba N, et al. Brain metabolism and diffusion in the rat cerebral cortex during pilocarpine-induced status epilepticus. Exp Neurol. 2008,209(1):145-154.
[21]Dalsgaard MK, Secher NH. The brain at work:a cerebral metabolic manifestation of central fatigue? J Neurosci Res.2007,85(15):3334-3339.
[22]Cavus I, Kasoff WS, CassadayMP, et al. Extracellular metabolites in the cortex and hippocampus of epileptic patients. Ann Neurol.2005,57(2):226-235.
[23]Oz G, Seaquist ER, Kumar A,et al. Human brain glycogen content and metabolism:implications on its role in brain energy metabolism. Am J Physiol Endocrinol Metab.2007,292(3):E946-951.
[24]Wiesinger H, Hamprecht B, Dringen R. Metabolic pathways for glucose in astrocytes. Glia.1997,21 (1):22-34.
[25]Pellerin L, Bouzier-Sore AK, Aubert A, et al. Activity-dependent regulation of energy metabolism by astrocytes:an update.Glia.2007,55(12):1251-1262.
[26]Rouach N, Koulakoff A, Abudara V, et al. Astroglial metabolic networks sustain hippocampal synaptic transmission. Science.2008,322(5907):1551-1555.
[27]Freund TF, Buzsaki G, Prohaska OJ, et al. Simultaneous recording of local electrical activity, partial oxygen tension and temperature in the rat hippocampus with a chamber-type microelectrode. Effects of anaesthesia, ischemia and epilepsy. Neuroscience.1989,28(3):539-549.
[28]Chapman AG, Meldrum BS, Siesjo BK. Cerebral metabolic changes during prolonged epileptic seizures in rats. J Neurochem.1977;28(5):1025-1035.
[29]Kloiber O, Bockhorst K, Hoehn-Berlage M, et al. Effect of hypoxia on bicuculline seizures of rat:NMR spectroscopy and bioluminescence imaging. NMR Biomed.1993,6(5):333-338.
[30]Yamada K, Ji JJ, Yuan H, et al. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science.2001,292(5521):1543-1546.
[31]Kirchner A, Veliskova J, Velisek L. Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitro. Eur J Neurosci.2006,23(6):1512-1522.
[32]Bainbridge JL, Gidal BE, Ryan M.The ketogenic diet. Central nervous system practice and research network of the american college of clinical pharmacy. Pharmacotherapy.1999,19(6):782-786.
[33]Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev.2009,59(2):293-315.
[34]Freeman JM, Vining EP, Pillas DJ, et al. The efficacy of the ketogenic diet-1998:a prospective evaluation of intervention in 150 children. Pediatrics.1998,102(6) :1358-1363.
[35]Bough KJ, Wetherington J, Hassel B,et al. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol.2006,60(2):223-235.
[36]Bough KJ, Gudi K, Han FT, et al. An anticonvulsant profile of the ketogenic diet in the rat. Epilepsy Res.2002,50(3):313-325.
[37]Yan QS, Jobe PC, Dailey JW. Noradrenergic mechanisms for the anticonvulsant effects of desipramine and yohimbine in genetically epilepsy-prone rats:studies with microdialysis. Brain Res.1993,610(1):24-31.
[38]Weinshenker D, Szot P. The role of catecholamines in seizure susceptibility: new results using genetically engineered mice. Pharmacol Ther.2002,94(3):213-233.
[39]Szot P, Weinshenker D, Rho JM, et al. Norepinephrine is required for the anticonvulsant effect of the ketogenic diet. Brain Res Dev Brain Res.2001,129 (2):211-214.
[40]Richichi C, Lin EJ, Stefanin D, et al. Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci.2004,24(12):3051-3059.
[41]Vezzani A, Sperk G. Overexpression of NPY and Y2 receptors in epileptic brain tissue:an endogenous neuroprotective mechanism in temporal lobe epilepsy? Neuropeptides.2004,38(4):245-252.
[42]Schlifke I, Kuteeva E, Hokfelt T, et al. Galanin expressed in the excitatory fibers attenuates synaptic strength and generalized seizures in the piriform cortex of mice. Exp Neurol.2006,200(2):398-406.
[43]Cheng CM, Hicks K, Wang J, et al. Caloric restriction augments brain glutamic acid decarboxylase-65 and -67 expression. J Neurosci Res.2004,77(2):270-276.
[44]Yudkoff M, Daikhin Y, Nissim I, et al. Effects of ketone bodies on astrocyte amino acid metabolism. J Neurochem.1997,69(2):682-692.
[45]Bough K. Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia.2008,49 Suppl 8:91-93.
[46]Huang YZ, McNamara JO. Inhibiting glycolysis to reduce seizures:how it might work. NatNeurosci.2006,9(11):1351-1352.
[47]Stafstrom CE, Ockuly JC, Murphree L, et al. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol.2009,65(4):435-447.
[48]Stafstrom CE, Roopra A, Sutula TP. Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia.2008,49 Suppl 8:97-100.
[49]Garriga-Canut M, Schoenike B, Qazi R, et al.2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci.2006,9(11):1382-1387
[50]Gasior M, Yankura J, Hartman AL, et al. Anticonvulsant and proconvulsant actions of 2-deoxy-D-glucose. Epilepsia.2010,51(8):1385-1394.
[51]Lian XY, Khan FA, Stringer JL. Fructose-1,6-bisphosphate has anticonvulsant activity in models of acute seizures in adult rats. J Neuroscience.2007,27(14):12007-12011.
[52]Fahlman CS, Bickler PE, Sullivan B, et al. Activation of the neuroprotective ERK signaling pathway by fructose-1,6-bisphosphate during hypoxia involves intracellular Ca2+ and phospholipase C. Brain Res.2002,958(1):43-51.
[53]Haglund MM, Schwartzkroin PA. Role of Na-K pump potassium regulation and IPSPs in seizures and spreading depression in immature rabbit hippocampal slices. J Neurophysiol.1990,63(2):225-239.
[54]Costa Leite T, Da Silva D, Guimaraes Coelho R, et al. Lactate favours the dissociation of skeletal muscle 6-phosphofructo-1-kinase tetramers down-regulating the enzyme and muscle glycolysis. Biochem J.2007,408(1):123-130.
[55]Kristensen M, Albertsen J, Rentsch M, et al. Lactate and force production in skeletal muscle. J Physiol.2005,562(Pt 2):521-526.
[56]Liou RS, Anderson S. Activation of rabbit muscle phosphofructokinase by F-actin and reconstituted thin filaments. Biochemistry.1980,19(12):2684-2688.
[57]Clarke F, Stephan P, Morton DJ, et al. The role of actin and associated structural proteins in the organization of glycolytic enzymes. In Actin:Structure and Function in Muscle and Non-Muscle Cells.12th International Congress of Biochemistry.1983,249-257 Sydney Australia
[58]Silva AP, Alves GG, Araujo AH, et al. Effects of insulin and actin on phosphofructokinase activity and cellular distribution in skeletal muscle. Ann Acad Bras Cienc.2004,76(3):541-548.
[59]Gomes Alves G, Sola-Penna M. Epinephrine modulates cellular distribution of muscle phosphofructokinase. Mol Genet Metab.2003,78(4):302-306.
[60]Zancan P, Sola-Penna M. Regulation of human erythrocyte metabolism by insulin:cellular distribution of 6-phosphofructo-l-kinase and its implication for red blood cell function. Mol Genet Metab.2005,86(3):401-411.
[61]Zancan P, Rosas AO, Marcondes MC, et al. Clotrimazole inhibits and modulates heterologous association of the key glycolytic enzyme 6-phosphofructo-1-kinase. Biochem Pharmacol.2007;73(10):1520-1527.
[62]Traynelis SF, Cull-Candy SG. Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons. Nature.1990,345(6273):347-350.
[63]Velisek L, Dreier JP, Stanton PK, et al. Lowering of extracellular pH suppresses low-Mg2+-induces seizures in combined entorhinal cortex-hippocampal slices. Exp Brain Res.1994,101(1):44-52.
[64]McKhann GM 2nd. Seizure termination by acidosis depends on ASIC1a. Neurosurgery.2008,63(4):N10.
[65]Waldmann R, Champigny G, Bassilana F, et al. A proton-gated cation channel involved in acid-sensing. Nature.1997,386(6621):173-177.
[66]Garcia-Anoveros J, Derfler B, Neville-Golden J, et al. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc Natl Acad Sci U S A.1997,94(4):1459-1464.
[67]Coryell MW, Ziemann AE, Westmoreland PJ, et al. Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit. Biol Psychiatry. 2007,62(10):1140-1148.
[68]Ziemann AE, Schnizler MK, Albert GW, et al. Seizure termination by acidosis depends on ASIC1a. Nat Neurosci.2008,11(7):816-822.
[69]Yin SH, Gong SS, Yan KS,et al. Effects of neuroglobin gene transfer in vivo on hearing response properties of neurons in the inferior colliculus in mice after administration of sodium salicylate. Sheng Li Xue Bao.2005,57(4):529-536.
[70]Faingold CL. Role of GABA abnormalities in the inferior colliculus pathophysiology-audiogenic seizures. Hear Res.2002,168(1-2):223-237.
[71]Storozhuk VM, Khorevin VI, Razumna NN, et al. The effects of activation of glutamate ionotropic connections of neurons in the sensorimotor cortex in a conditioned reflex. Neurosci Behav Physiol.2003,33(5):479-488.
[72]Chen JC, Chesler M.Modulation of extracellular pH by glutamate and GABA in rat hippocampal slices.J Neurophysiol.1992,67(1):29-36.
[73]Sloviter RS, Dichter MA, Rachinsky TL,et al. Basal expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus. J Comp Neurol.1996,373(4):593-618.
[74]Somjen GG. Acidification of interstitial fluid in hippocampal formation caused by seizures and by spreading depression. Brain Res.1984,311(1):186-188.
[75]Wang RI, Sonnenschein RR. PH of Cerebral cortex during induced convulsions. J Neurophysiol.1955,18(2):130-137.
[76]Wemmie JA, Chen J, Askwith CC,et al. The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Neuron.2002,34(3):463-477.
[77]Xiong ZG, Zhu XM, Chu XP, et al. Neuroprotection in ischemia:blocking calcium-permeable acid-sensing ion channels. Cell.2004; 118(6):687-698.
[78]Somjen GG, Tombaugh GC. pH modulation of neuronal excitability and central nervous system functions. In:Kaila K, Ransom BR, ed. pH and Brain Function. New York:Wiley-Leiss Inc.1998.
[79]Velisek L. Extracellular acidosis and high levels of carbon dioxide suppress synaptic transmission and prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices. Hippocampus.1998,8(1):24-32.
[80]Stringer JL, Xu K. Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphate. Epilepsia.2008,49 Suppl 8:101-103.
[81]Abe K, Nakanishi K, Saito H. The possible role of endogenous glutathione as an anticonvulsant in mice. Brain Res.2000,854(1-2):235-238.
[82]Vexler ZS, Wong A, Francisco C, et al. Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress. Brain Res.2003,960(1-2):90-98.
[1]Scharfman HE. The neurobiology of epilepsy[J]. Curr Neurol Neurosci Rep, 2007,7(4):348-354.
[2]Berg AT. Defining intractable epilepsy.Adv Neurol.2006,97:5-10.
[3]Vining EP. Clinical efficacy of the ketogenic diet.Epilepsy Res.1999,37(3):181-190.
[4]Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007,48(1):43-58.
[5]Huttenlocher PR. Ketonemia and seizures:metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy. Pediatr Res.1976,10(5):536-540.
[6]Gasior M, Yankura J, Hartman AL, et al. Anticonvulsant and proconvulsant actions of 2-deoxy-D-glucose. Epilepsia.2010,51(8):1385-1394.
[7]Stringer JL, Xu K. Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphate. Epilepsia.2008,49 Suppl 8:101-103.
[8]Stafstrom CE, Ockuly JC, Murphree L, et al. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol.2009,65(4):435-447.
[9]Stafstrom CE, Roopra A, Sutula TP. Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia.2008,49 Suppl 8:97-100.
[10]Garriga-Canut M, Schoenike B, Qazi R, et al.2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci.2006,9(11):1382-1387.
[11]Gasior M, Yankura J, Hartman AL, et al. Anticonvulsant and proconvulsant actions of 2-deoxy-D-glucose. Epilepsia.2010,51(8):1385-1394.
[12]Huang YZ, McNamara JO. Inhibiting glycolysis to reduce seizures:how it might work. Nat Neurosci.2006,9(11):1351-1352.
[13]Rebecchi MJ, Pentyala SN. Structure, function, and control of phosphoinositide-specific phospholipase C.Physiol Rev.2000,80(4):1291-1335.
[14]Fukami K.Structure, regulation, and function of phospholipase C isozymes.J \Biochem.2002,131(3):293-299.
[15]Offermanns S, Toombs CF, Hu YH, et al.Defective platelet activation in G alpha(q)-deficient mice.Nature.1997,389(6647):183-186.
[16]Carpenter G, Ji Qs.Phospholipase C-gamma as a signal-transducing element.
Exp Cell Res.1999,253(1):15-24.
[17]Essen LO, Perisic O, Cheung R, et al.Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.Nature.1996,380(6575):595-60.
[18]Ferguson KM, Lemmon MA, Schlessinger J, et al. Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain.Cell.1995,83(6):1037-46.
[19]Noh DY, Shin SH, Rhee SG.Phosphoinositide-specific phospholipase C and mitogenic signaling. Biochim Biophys Acta.1995,1242(2):99-113.
[20]Rhee SG, Choi KD.Regulation of inositol phospholipid-specific phospholipase C isozymes.J Biol Chem.1992,267(18):12393-12396.
[21]Ye K, Aghdasi B, Luo HR, et al. Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE.Nature.2002,415(6871):541-544.
[22]Binder DK, Routbort MJ, McNamara JO. Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus. J Neurosci.1999,19 (11):4616-4626.
[23]Rivera C, Voipio J, Thomas-Crusells J, et al. Mechanism of activity-down regulation of the neuron-specific K-Cl cotransporter KCC2.J Neurosci.2004, 24(19):4683-4691.
[24]He XP, Minichiello L, Klein R, et al. Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus. J Neurosci.2002,22 (17):7502-7508.
[25]He XP,Pan E,Sciarretta C,et al. Disruption of trkB-mediated PLCy signaling inhibits limbic epileptogenesis. J Neurosci.2010,30 (18):6188-6196.
[26]ExtonJH. Signaling through PhosPhatidyleholine breakdown. JBiol Chem.1990,265(l):1-4.
[27]Nishizuka Y, Takai Y, Kishimoto A, et al.A role of calcium in the activation of a new protein kinase system. Adv Cyclic Nucleotide Res.1978,9:209-220.
[28]Adams JM, Cory S.The Bcl-2 protein family:arbiters of cell survival.Science.1998,281(5381):1322-6.
[29]Azzi A, Boscoboinik D, Hensey C.The protein kinase C family. Eur J Biochem.1992,208(3):547-557.
[30]Niimura M, Moussa R, Bissoon N, et al. Changes in phosphorylation of the NMDA receptor in the rat hippocampus induced by status epilepticus.J Neurochem. 2005,92(6):1377-1385.
[31]Silva AP,Lourenco J,Xapelli S,et al.Protein kinase C activity blocks neuropeptide Y-mediated inhibition of glutamate release and contributes to excitability of the hippocampus in status epilepticus.FASEB J.2007,21(3):671-681.
[32]Fuortes MG, Faria LC, Merlin LR. Impact of protein kinase C activation on epileptiform activity in the hippocampal slice.Epilepsy Res.2008,82(1):38-45.
[33]Rodrigo GC, Standen NB, ATP-sensitive potassium channels. Curr Pharm Des.2005,11(15):1915-1940.
[34]Tucker SJ, Gribble FM, Proks P, Molecular determinants of KATP channel inhibition by ATP.EMBO J.1998,17(12):3290-3296.
[35]Kristiansen SB, Henning O, Kharbanda RK, et al. Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol.2005,288(3):H1252-1256.
[36]Blandini F, Nappi G, Tassorelli C, Martignoni E. Functional changes of the basal ganglia circuitry in Parkinson's disease. Prog Neurobiol.2000,62(1):63-88.
[37]Kimura S,Zhang GX,Nishiyama A, et al. Role of NAD(P)H oxidase- and mitochondria-derived reactive oxygen species in cardioprotection of ischemic reperfusion injury by angiotensin II. Hypertension.2005,45(5):860-866.
[38]Zhou M, Tanaka O, Suzuki M, et al. Localization of pore-forming subunit of the ATP-sensitive K(+)-channel, Kir6.2, in rat brain neurons and glial cells. Brain Res Mol Brain Res.2002,101(1-2):23-32.
[39]Liss B, Bruns R, Roeper J. Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. EMBO J.1999,18(4):833-846.
[40]Miki T, Liss B, Minami K, ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci. 2001,4(5):507-512.
[41]Curia G, Longo D, Biagini Q Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods.2008,172:143-157
[42]Landfield PW. Aging-related increase in hippocampal calcium channels.Life Sci.1996,59(5-6):399-404.
[43]Gloveli T, Schmitz D, Heinemann U. Interaction between superficial layers of the entorhinal cortex and the hippocampus in normal and epileptic temporal lobe.Epilepsy Res.1998,32(1-2):183-193.
[44]Grassi S, Pettorossi VE. Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.Prog Neurobiol.2001,64(6):527-553.
[45]Jiruska P, Csicsvari J, Powell AD, et al. High-frequency network activity, global increase in neuronal activity, and synchrony expansion precede epileptic seizures in vitro. J Neurosci.2010,30(16):5690-5701.
[46]Neher E, Sakmann B.Single-channel currents recorded from membrane of denervated frog muscle fibres.Nature.1976.260(5554):799-802.
[47]Edwards FA, Konnerth A, Sakmann B, et al. A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system.Pflugers Arch.1989,414(5):600-612.
[48]Dubinsky WP,Mayorga-Wark O,Schultz SG.Colocalization of glycolytic enzyme activity and KATP channels in basolateral membrane of Necturus enterocytes.Am J Physiol.1998,275:C1653-1659.
[49]Mercer RW, Dunham PB. Membrane-bound ATP fuels the Na/K pump. Studies on membrane-bound glycolytic enzymes on inside-out vesicles from human red cell membranes. J Gen Physiol.1981,78 (5):547-568.
[50]Ma W, Berg J, Yellen G. Ketogenic diet metabolites reduce firing in central neurons by opening K (ATP) channels.J Neurosci.2007,27 (14):3618-3625.
[51]Aziz Q, Thomas AM, Khambra T, et al. Regulation of the ATP-sensitive
Potassium Channel Subunit, Kir6.2, by a Ca2+-dependent Protein Kinase C.J Biol Chem.2012,287(9):6196-6207.
[52]Shi Y, Cui N, Shi W, et al. A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the vascular KATP channel inhibition by protein kinase C. J Biol Chem.2008,283(5):2488-2494.
[53]Park WS, Ko EA, Han J, et al. Endothelin-1 acts via protein kinase C to block KATP channels in rabbit coronary and pulmonary arterial smooth muscle cells. J Cardiovasc Pharmacol.2005,45(2):99-108.
[54]Shi Y, Cui N, Shi W, et al. A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the vascular KATP channel inhibition by protein kinase C. J Biol Chem.2008,283(5):2488-2494.
[55]Di Paolo G, De Camilli PPhosphoinositides in cell regulation and membrane dynamics.Nature.2006,443(7112):651-657.
[56]Krauss M, Haucke V. Phosphoinositide-metabolizing enzymes at the interface between membrane traffic and cell signalling. EMBO Rep.2007, 8(3):241-246.
[57]Quinn KV, Cui Y, Giblin JP, et al. Do anionic phospholipids serve as cofactors or second messengers for the regulation of activity of cloned ATP-sensitive K+channels? Circ Res.2003,93(7):646-655.
[58]Zeng WZ, Li XJ, Hilgemann DW,et al.Protein kinase C inhibits ROMK1 channel activity via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. J Biol Chem.2003,278(19):16852-16856.
[59]Nasuhoglu C, Feng S, Mao Y, et al. Modulation of cardiac PIP2 by cardioactive hormones and other physiologically relevant interventions.Am J Physiol Cell Physiol.2002,283(1):C223-234.