Prevention of adenosine A2A receptor activation diminishes beat-to-beat alternation in human atrial myocytes
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- 作者：Cristina E. Molina ; Anna Llach ; Adela Herraiz-Mart铆nez…
- 关键词：Adenosine receptor ; Atrial myocyte ; Electrophysiology ; l ; Type calcium current ; Sarcoplasmic reticulum
- 刊名：Basic Research in Cardiology
- 出版年：2016
- 出版时间：January 2016
- 年：2016
- 卷：111
- 期：1
- 全文大小：2,468 KB
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Anna Llach (2)
Adela Herraiz-Mart铆nez (1)
Carmen Tarifa (1)
Montserrat Barriga (1)
Rob F. Wiegerinck (2)
Jacqueline Fernandes (2)
Nuria Cabello (1)
Alex Vallmitjana (4)
Ra煤l Benit茅z (4)
Jos茅 Montiel (3)
Juan Cinca (2)
Leif Hove-Madsen (1)
1. Cardiac Rhythm and Contraction, Cardiovascular Research Centre CSIC-ICCC and IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni M陋 Claret 167, 08025, Barcelona, Spain
5. Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, 45122, Essen, Germany
2. Department of Cardiology and IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
4. Department of Automatic Control, Universitat Polit猫cnica de Catalunya, Barcelona, Spain
3. Department of Cardiac Surgery and IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Cardiology - 出版者：Springer Berlin / Heidelberg
- ISSN：1435-1803
文摘
Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 卤 0.1 to 0.6 卤 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 卤 0.1 to 0.5 卤 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 卤 3 to 51 卤 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 卤 0.12 to 1.86 卤 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 卤 0.1 to 1.2 卤 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation. Keywords Adenosine receptor Atrial myocyte Electrophysiology l-Type calcium current Sarcoplasmic reticulum