Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation
Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation
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DOI：
10.1093/eurheartj/ehn140
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发表时间：
2008-05-01
影响因子：
39.3
通讯作者：
Hatem, Stephane N.
中科院分区：
文献类型：
--
作者：
Dinanian, Sylvie;Boixel, Christophe;Hatem, Stephane N.
L型钙电流（I-CaL）降低是心房颤动（AF）发生的重要机制。在这里，我们的目的是确定致病因素与I-CaL downregulation.Methods和结果心房肌细胞分离右心房附件从86例成人患者窦性心律冠状动脉疾病，主动脉瓣疾病，或二尖瓣疾病（MVD）。用全细胞膜片钳技术记录离体心肌细胞的电流。在172个研究的心肌细胞中记录的I-CaL显示出显著的峰密度变化，范围从0.1到9.0 pA/pF. I-CaL峰密度与膜电容或当前生物物理特性的变化无关。对于给定样品，I-CaL峰密度是均匀的。在MVD或左室射血分数低（< 45%）的患者中记录到较小的I-CaL值。小的I-CaL值更敏感的β-肾上腺素能激动剂，异丙肾上腺素（1 μ M），和磷酸二酯酶抑制剂，3-异丁基-1-甲基-黄嘌呤（10 μ M）。结论在人类心房肌细胞，I-CaL的变异性与供体的临床病史。在房颤高风险窦性心律患者中已经观察到I-CaL下调，并且与对β-肾上腺素能激动剂的最大反应相关。
Aims A decrease in L-type calcium current (I-CaL) is an important mechanism favouring atrial fibrillation (AF). Here, we aimed to identify pathogenic factors associated with I-CaL downregulation.Methods and results Atrial myocytes were isolated from right atrial appendages obtained from 86 adult patients in sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (MVD). Current was recorded in isolated myocytes using the whole-cell patch-clamp technique. The I-CaL recorded in the 172 myocytes studied showed a marked variability of peak density ranging from 0.1 to 9.0 pA/pF. The I-CaL peak density did not correlate with membrane capacitance or changes in current biophysical properties. The I-CaL peak density was homogeneous for a given sample. Small I-CaL values were recorded in patients with MVD or with a low left ventricular ejection fraction (< 45%). Small I-CaL values were more sensitive to the beta-adrenergic agonist, isoproterenol (1 mu M), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 mu M).Conclusion In human atrial myocytes, the variability of I-CaL is related to the clinical history of the donors. The downregulation of I-CaL is already observed in patients in sinus rhythm with a high risk of AF and is associated with the greatest response to beta-adrenergic agonist.