Kondo Richard P, Dederko Dorothy A, Teutsch Christine, Chrast Jacqueline, Catalucci Daniele, Chien Kenneth R, Giles Wayne R
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
J Physiol. 2006 Feb 15;571(Pt 1):131-46. doi: 10.1113/jphysiol.2005.101428. Epub 2005 Dec 15.
In the mammalian heart, the right ventricle (RV) has a distinct structural and electrophysiological profile compared to the left ventricle (LV). However, the possibility that myocytes from the RV and LV have different contractile properties has not been established. In this study, sarcomere shortening, [Ca2+]i transients and Ca2+ and K+ currents in unloaded myocytes isolated from the RV, LV epicardium (LVepi) and LV endocardium (LVendo) of adult mice were evaluated. Maximum sarcomere shortening elicited by field stimulation was graded in the order: LVendo > LVepi > RV. Systolic [Ca2+]i was higher in LVendo myocytes than in RV myocytes. Voltage-clamp experiments in which action potential (AP) waveforms from RV and LVendo were used as the command signal, demonstrated that total Ca2+ influx and myocyte shortening were larger in response to the LVendo AP, independent of myocyte subtypes. Evaluation of possible regional differences in myocyte Ca2+ handling was based on: (i) the current-voltage relation of the Ca2+ current; (ii) sarcoplasmic reticulum Ca2+ uptake; and (iii) mRNA expression of important components of the Ca2+ handling system. None of these were significantly different between RV and LVendo. In contrast, the Ca2+-independent K+ current, which modulates AP repolarization, was significantly different between RV, LVepi and LVendo. These results suggest that these differences in K+ currents can alter AP duration and modulate the [Ca2+]i transient and corresponding contraction. In summary, these findings provide an initial description of regional differences in excitation-contraction coupling in the adult mouse heart [corrected]
在哺乳动物心脏中,右心室(RV)与左心室(LV)相比具有独特的结构和电生理特征。然而,右心室和左心室的心肌细胞是否具有不同的收缩特性尚未确定。在本研究中,对从成年小鼠的右心室、左心室心外膜(LVepi)和左心室心内膜(LVendo)分离的无负荷心肌细胞的肌节缩短、[Ca2+]i瞬变以及Ca2+和K+电流进行了评估。场刺激引起的最大肌节缩短程度依次为:LVendo > LVepi > RV。LVendo心肌细胞的收缩期[Ca2+]i高于RV心肌细胞。以右心室和LVendo的动作电位(AP)波形作为指令信号进行的电压钳实验表明,无论心肌细胞亚型如何,对LVendo AP的反应中总Ca2+内流和心肌细胞缩短幅度更大。基于以下几点对心肌细胞Ca2+处理的可能区域差异进行了评估:(i)Ca2+电流的电流-电压关系;(ii)肌浆网Ca2+摄取;(iii)Ca2+处理系统重要成分的mRNA表达。右心室和LVendo之间这些方面均无显著差异。相反,调节AP复极化的非Ca2+依赖性K+电流在右心室、LVepi和LVendo之间存在显著差异。这些结果表明,K+电流的这些差异可改变AP持续时间,并调节[Ca2+]i瞬变及相应的收缩。总之,这些发现初步描述了成年小鼠心脏兴奋-收缩偶联的区域差异[已修正]