Wetzel G T, Klitzner T S
Department of Pediatrics, University of California at Los Angeles 90095, USA.
Cardiovasc Res. 1996 Feb;31 Spec No:E52-60.
This overview of cardiac ion channel development does not suggest any particular theme underlying the expression or regulation of all channel subtypes. Calcium and potassium channels generally exhibit increased expression in more mature hearts. However, this increase in channel number or activity as determined under voltage clamp conditions may not be translated into increased activity in vivo. Concomitant changes in other physiological factors such as local intracellular Ca2+ accumulation, increased resting membrane potential and decreased heart rate in mature heart may inhibit or augment channel activity. Na(+)-Ca2+ exchange activity appears to decrease with development, possibly reflecting its decreasing role in both systolic and diastolic Ca2+ regulation. Na+ channel activity follows a middle course, exhibiting little change in channel conductance. The reported shift in the voltage dependence of channel inactivation toward more negative membrane potentials may reflect a concomitant shift in the resting membrane potential in mature heart. However, this change is in the direction opposite to that reported for L-type Ca2+ channel inactivation, suggesting that the regulation of these channels is not modulated by a common factor such as membrane surface charge. A detailed characterization of multiple channel subtypes in mature myocardium has resulted in significant advances in models of the cardiac action potential and excitation-contraction coupling. Recently, developmental changes in ion channel physiology have been described, setting the stage for a comparable elucidation of the ontogeny of the cardiac action potential. Ca2+ and K+ channel currents generally become more prominent with development. In contrast, developmental changes in Na+ currents are less dramatic and Na(+)-Ca2+ exchange currents appear to decrease with age. These changes may, in part, be reflected by the increasingly important role of transsarcolemmal Ca2+ influx in triggering Ca2+ release from the SR in mature heart as compared to its direct role of providing Ca2+ for cell contraction in immature heart. These developmental changes in ion channel expression and function are likely to have a significant effect on the generation of the action potential in individual myocytes. Developmental changes in the characteristics of the action potential may then have a major influence on the initiation, propagation and termination of autonomic, triggered, and re-entrant arrhythmias. Progress in this area provides an essential foundation for the evolution of a systematic approach to pediatric arrhythmias comparable to that under development for mature heart [3].
这篇关于心脏离子通道发育的综述并未表明所有通道亚型的表达或调控存在任何特定主题。钙通道和钾通道通常在更成熟的心脏中表达增加。然而，在电压钳条件下确定的通道数量或活性的这种增加，在体内可能不会转化为活性增加。成熟心脏中其他生理因素的伴随变化，如局部细胞内Ca2+积累、静息膜电位增加和心率降低，可能会抑制或增强通道活性。钠钙交换活性似乎随着发育而降低，这可能反映了其在收缩期和舒张期Ca2+调节中作用的减弱。钠通道活性呈中等变化，通道电导变化不大。报道的通道失活电压依赖性向更负膜电位的转变，可能反映了成熟心脏静息膜电位的伴随转变。然而，这种变化的方向与L型钙通道失活报道的方向相反，表明这些通道的调节不是由膜表面电荷等共同因素调节的。对成熟心肌中多种通道亚型的详细表征，已在心脏动作电位和兴奋-收缩偶联模型方面取得了重大进展。最近，已经描述了离子通道生理学的发育变化，为类似地阐明心脏动作电位的个体发生奠定了基础。钙通道和钾通道电流通常随着发育而变得更加突出。相比之下，钠电流的发育变化不太显著，钠钙交换电流似乎随着年龄增长而降低。与未成熟心脏中钠钙交换直接为细胞收缩提供Ca2+的作用相比，成熟心脏中跨肌膜Ca2+内流在触发肌浆网释放Ca2+方面的作用日益重要，这些变化可能部分反映了这一点。离子通道表达和功能的这些发育变化可能对单个心肌细胞动作电位的产生产生重大影响。动作电位特征的发育变化可能进而对自主、触发和折返性心律失常的起始、传播和终止产生重大影响。该领域的进展为制定一种系统的儿科心律失常研究方法提供了重要基础，这种方法类似于正在为成熟心脏开发的方法[3]。
