Relationship Between Gap-Junctional Conductance and Conduction Velocity in Mammalian Myocardium
Relationship Between Gap-Junctional Conductance and Conduction Velocity in Mammalian Myocardium
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DOI：
10.1161/circep.113.000848
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发表时间：
2013-12-01
影响因子：
8.4
通讯作者：
Peters，Nicholas S.
中科院分区：
文献类型：
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作者：
Dhillon，Paramdeep S.;Gray，Rosaire;Peters，Nicholas S.
背景隙结电阻率Rj被认为是传导速度（CV）的关键决定因素。然而，对连接蛋白基因敲除小鼠的研究表明，只有连接蛋白几乎完全缺失时，CV才会显著减慢，这些发现导致了心肌间隙连接显著冗余的概念。我们挑战了这一流行的概念，并提出了在人类和豚鼠心肌中分别独立测量的rh和CV之间存在连续关系的假设。方法和结果采用油隙阻抗和微电极技术直接测量肥厚性心肌病患者左心室心肌和豚鼠心房和心室心肌在20µmol/L卡苯诺酮药物解耦前和解耦期间的rv和CV。人、豚鼠心肌、卡贝诺洛酮治疗前后的rh和CV呈连续相关（r2=0.946；P<0.01）。在豚鼠左心室、左心房和右心房，卡贝诺龙分别使drj28±9%、26±16%和25±14%升高，使CV降低17±3%、23±8%和11±4%（与对照组相比，p <0.05）。卡贝诺洛酮可延长右心房（39.7±4.2 ~ 42.3±4.3 ms， P=0.01）和右心室（48.1±2.5 ~ 53.3±5.3 ms， P<0.01）电图持续时间。结论心脏腔室和不同物种间的心室电位和心室电位之间存在连续的关系，表明细胞偶联的自然变化可以解释心室电位的变化，并且存在大量冗余偶联的概念是站不住脚的。
BackgroundGap junction resistivity,Rj, has been proposed as a key determinant of conduction velocity (CV). However, studies in connexin-gene knockout mice demonstrated significant CV slowing only with near-complete connexin deletion, and these findings led to the concept of a significant redundancy of myocardial gap junctions. We challenged this prevailing concept and addressed the hypothesis that there is a continuous relationship betweenRjand CV, each independently measured in human and guinea-pig myocardium.Methods and ResultsRjand CV were directly measured by oil-gap impedance and microelectrode techniques in human left ventricular myocardium from patients with hypertrophic cardiomyopathy and in guinea-pig atrial and ventricular myocardium before and during pharmacological uncoupling with 20-µmol/L carbenoxolone. There was a continuous relationship betweenRjand CV in human and guinea-pig myocardium, pre- and post-carbenoxolone (r2=0.946;P<0.01). In guinea-pig left ventricle, left atrium, and right atrium, carbenoxolone increasedRjby 28±9%, 26±16%, and 25±14% and slowed CV by 17±3%, 23±8%, and 11±4% respectively (allP<0.05 versus control). As a clinically accessible measure of local microscopic myocardial conduction slowing in vivo in the intact human heart, carbenoxolone prolonged electrogram duration in the right atrium (39.7±4.2 to 42.3±4.3 ms;P=0.01) and right ventricle (48.1±2.5 to 53.3±5.3 ms;P<0.01).ConclusionsThere is a continuous relationship betweenRjand CV that is consistent between cardiac chambers and across species, indicating that naturally occurring variations in cellular coupling can account for variations in CV, and that the concept that there is massive redundancy of coupling is not tenable.