L-type Ca²⁺ channel activity determines modulation of GABA release by dopamine in the substantia nigra reticulata and the globus pallidus of the rat

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• 作者：S. Recillas-Morales ; L. S谩nchez-Vega ; N. Ochoa-S谩nchez ; I. Caballero-Flor谩n ; F. Paz-Berm煤dez ; I. Silva ; J. Aceves ; D. Erlij ; B. Flor谩n
• 关键词：A2ARs ; adenosine A2A receptors ; ACSF ; artificial cerebrospinal fluid ; D1Rs ; dopamine D1 receptors ; Enk+ ; enkephaline ; GP ; globus pallidus ; GPe ; external GP ; MSNs ; medium spiny neurons ; SNr ; substantia nigra pars reticulata
• 刊名：Neuroscience
• 出版年：3 January, 2014
• 年：2014
• 卷：256
• 期：Complete
• 页码：292-301
• 全文大小：1410 K

文摘

Modulation of L-type Ca²⁺-channel function by dopamine is a major determinant of the rate of action potential firing by striatal medium spiny neurons. However, the role of these channels in modulating GABA release by nerve terminals in the basal ganglia is unknown. We found that depolarization-induced [³H]GABA release in both the substantia nigra reticulata and the external globus pallidus (GPe), was depressed by about 50% by either the selective L-channel dihydropyridine blocker nifedipine or the P/Q channel blocker 蠅-agatoxin TK. The effects of these blockers were additive and together eliminated about 90% of depolarization-induced [³H]GABA release. In addition, in the substantia nigra reticulata, dihydropyridines prevented both the stimulation of [³H]GABA release produced by dopamine D1 receptor activation and the inhibition caused by D4 receptor activation. In the GP nifedipine blocked the effects of D2 and A2_A receptor coactivation as well as the effects of activating adenylyl cyclase with forskolin. 蠅-Agatoxin TK did not interfere with the action of these modulatory agents. The L-type Ca²⁺-channel agonist BAYK 8644 stimulated GABA release in both substantia nigra reticulata and GP. Because dihydropyridine sensitivity is a key criterion to identify L-type Ca²⁺-channel activity, our results imply that these channels are determinant of GABA release modulation by dopamine in striatonigral, striatopallidal and pallidonigral terminals.