Na+ channel distribution and electrophysiological heterogeneities in guinea pig ventricular wall
Na+ channel distribution and electrophysiological heterogeneities in guinea pig ventricular wall
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DOI：
10.1152/ajpheart.00816.2010
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发表时间：
2011-03-01
影响因子：
4.8
通讯作者：
Olesen, Soren Peter
中科院分区：
文献类型：
--
作者：
Osadchii, Oleg E.;Soltysinska, Ewa;Olesen, Soren Peter
张建军，张建军，张建军。豚鼠脑室壁钠离子通道分布及电生理异质性。[J]中国生物医学工程学报，2016,31(2):389 - 391。首次发表于2010年12月24日；doi: 10.1152 / ajpheart.00816.2010。我们试图在豚鼠心脏中探索钠离子通道穿过心室壁的分布模式，并确定其功能相关性。采用Western blotting法测定心室组织跨壁样品中电压依赖性Na+通道（Na-v）蛋白表达水平。使用分离的灌注心脏制剂记录单相动作电位和容积传导心电图，测量有效不应期（ERPs）和起搏阈值，以评估心外膜和心内膜刺激部位的兴奋性、电恢复动力学和刺激诱发的快速心律失常的易感性。在两个心室，Na-v蛋白在心内膜的表达高于心外膜，心肌中层表达水平中等。心内膜刺激部位表现出较高的兴奋性，表现为常规刺激时起搏阈值较低，收缩外刺激后重建的强度-间期曲线较心外膜向下移位。在大范围起搏速率下评估的ERP恢复显示心内膜比心外膜刺激部位更大的最大斜率和更快的动力学。钠离子通道阻滞剂Flecainide降低了最大ERP恢复斜率，减缓了恢复动力学，消除了心外膜与心内膜电恢复动力学的差异。更大的兴奋性和更陡的电恢复与心内膜比心外膜更大的心律失常易感性相关，这可以通过测量心室颤动阈值、快速心脏起搏引起的快速心律失常的诱导性和刺激诱发的复极化交替的幅度来评估。综上所述，较高的Na+通道表达水平可能导致豚鼠心脏更大的兴奋性、更陡的电恢复斜率和更快的恢复动力学，以及对刺激诱发的心内膜速性心律失常更敏感。
Osadchii OE, Soltysinska E, Olesen SP. Na+ channel distribution and electrophysiological heterogeneities in guinea pig ventricular wall. Am J Physiol Heart Circ Physiol 300: H989-H1002, 2011. First published December 24, 2010; doi: 10.1152/ajpheart.00816.2010.-We sought to explore the distribution pattern of Na+ channels across ventricular wall, and to determine its functional correlates, in the guinea pig heart. Voltage-dependent Na+ channel (Na-v) protein expression levels were measured in transmural samples of ventricular tissue by Western blotting. Isolated, perfused heart preparations were used to record monophasic action potentials and volume-conducted ECG, and to measure effective refractory periods (ERPs) and pacing thresholds, in order to assess excitability, electrical restitution kinetics, and susceptibility to stimulation-evoked tachyarrhythmias at epicardial and endocardial stimulation sites. In both ventricular chambers, Na-v protein expression was higher at endocardium than epicardium, with midmyocardial layers showing intermediate expression levels. Endocardial stimulation sites showed higher excitability, as evidenced by lower pacing thresholds during regular stimulation and downward displacement of the strength-interval curve reconstructed after extrasystolic stimulation compared with epicardium. ERP restitution assessed over a wide range of pacing rates showed greater maximal slope and faster kinetics at endocardial than epicardial stimulation sites. Flecainide, a Na+ channel blocker, reduced the maximal ERP restitution slope, slowed restitution kinetics, and eliminated epicardial-to-endocardial difference in dynamics of electrical restitution. Greater excitability and steeper electrical restitution have been associated with greater arrhythmic susceptibility of endocardium than epicardium, as assessed by measuring ventricular fibrillation threshold, inducibility of tachyarrhythmias by rapid cardiac pacing, and the magnitude of stimulation-evoked repolarization alternans. In conclusion, higher Na+ channel expression levels may contribute to greater excitability, steeper electrical restitution slopes and faster restitution kinetics, and greater susceptibility to stimulation-evoked tachyarrhythmias at endocardium than epicardium in the guinea pig heart.