Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release
Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release
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DOI：
10.1016/j.cardiores.2006.07.020
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发表时间：
2006-11-01
影响因子：
10.8
通讯作者：
Franco, Rafael
中科院分区：
文献类型：
--
作者：
Hove-Madsen, Leif;Prat-Vidal, Cristina;Franco, Rafael
背景资料：心脏兰尼碱受体（RyR 2）的环腺苷酸依赖性调节的改变已被认为是心力衰竭、室性快速性心律失常和房颤患者肌浆网（SR）自发钙释放增加的原因。腺苷A（2A）受体（adenosine A（2A）receptor，A（2A）R）是一种调节cAMP水平的受体，但其在人心肌细胞中的表达和功能尚未见报道。A（2A）R在人右心房中表达，并沿着Z线呈带状分布，与兰尼碱受体重叠。A（2A）R刺激可引起离体人心房肌细胞自发SR钙释放的蛋白激酶A依赖性增加。A（2A）R激动剂CGS 21680将钙火花的频率从0.12 +/- 0.03增加到0.31 +/- 0.08火花。μ m min（-1）（P < 0.05）;钙波从0.65 ± 0.31到5.11 ± 1.84波（.）min（-1）（p < 0.03）。此外，自发钠钙交换电流（I-NCX）从1.19 +/- 0.17增加到2.50 +/- 0.42 min（-1）（p < 0.001）。相反，CGS 21680没有改变咖啡因诱导的钙释放（6.98 +/- 0.52 vs. 6.82 +/- 0.57 antol pF（-1），p=0.6）或自发I-NCX振幅（0.32 +/- 0.05 vs. 0.29 +/- 0.04 pA pF（-1），p=0.2）。L-型钙电流的电流-电压关系和幅度（1.62 +/- 0.18 vs. 1.80 +/- 0.18 pA pF（-1））没有改变，但CGS 21680的钙释放依赖性失活更快（13.4 +/- 0.7 vs. 15.8 +/- 1.0 ms，p < 0.001）.结论：腺苷A2 A受体在人心房心肌中表达，并调节SR自发钙释放的频率.（c）2006欧洲心脏病学会.出版社：Elsevier B.V版权所有。
Background: Alterations in the cyclic AMP-dependent regulation of the cardiac ryanodine receptor (RyR2) have been proposed to account for increased spontaneous calcium release from the sarcoplasmic reticulum (SR) in patients with heart failure, ventricular tachyarrhythmias and atrial fibrillation. While the adenosine A(2A) receptor (A(2A)R) is known to regulate cyclic AMP levels, expression and function of this receptor in human cardiac myocytes has not been investigated.Methods: PCR, western blotting and immunofluorescence were used to identify the A(2A)R, and functional effects of A(2A)R stimulation were measured with confocal calcium imaging and patch-clamp technique.Results: The A(2A)R is expressed in the human right atrium and distributed in a banded pattern along the Z-lines, overlapping with the ryanodine receptor. A(2A)R stimulation caused a protein kinase A dependent increase in spontaneous SR calcium release in isolated human atrial myocytes. The A(2A)R agonist CGS21680 increased the frequency of calcium sparks from 0.12 +/- 0.03 to 0.31 +/- 0.08 sparks(.)mu m min(-1) (p < 0.05) and calcium waves from 0.65 +/- 0.31 to 5.11 +/- 1.84 waves(.)min(-1) (p < 0.03). Moreover, spontaneous Na-Ca exchange currents (I-NCX) increased from 1.19 +/- 0.17 to 2.50 +/- 0.42 min(-1) (p < 0.001). In contrast, CGS21680 did not alter caffeine inducible calcium release (6.98 +/- 0.52 vs. 6.82 +/- 0.57 antol pF(-1), p=0.6) or the spontaneous I-NCX amplitude (0.32 +/- 0.05 vs. 0.29 +/- 0.04 pA pF(-1), p=0.2). Current-voltage relationship and amplitude of the L-type calcium current (1.62 +/- 0.18 vs. 1.80 +/- 0.18 pA pF(-1)) were not altered, but calcium release dependent inactivation was faster with CGS21680 (13.4 +/- 0.7 vs. 15.8 +/- 1.0 ms, p < 0.001).Conclusions: Adenosine A2A receptors are expressed in the human atrial myocardium and modulate the frequency of spontaneous calcium release from the SR. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved.