Grandy Scott A, Trépanier-Boulay Véronique, Fiset Céline
Research Center, Montreal Heart Institute, and Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2168-77. doi: 10.1152/ajpheart.00521.2007. Epub 2007 Aug 3.
To better understand the mechanisms that underlie cardiac repolarization abnormalities in the immature heart, this study characterized and compared K(+) currents in mouse ventricular myocytes from day 1, day 7, day 20, and adult CD1 mice to determine the effects of postnatal development on ventricular repolarization. Current- and patch-clamp techniques were used to examine action potentials and the K(+) currents underlying repolarization in isolated myocytes. RT-PCR was used to quantify mRNA expression for the K(+) channels of interest. This study found that action potential duration (APD) decreased as age increased, with the shortest APDs observed in adult myocytes. This study also showed that K(+) currents and the mRNA relative abundance for the various K(+) channels were significantly greater in adult myocytes compared with day 1 myocytes. Examination of the individual components of total K(+) current revealed that the inward rectifier K(+) current (I(K1)) developed by day 7, both the Ca(2+)-independent transient outward current (I(to)) and the steady-state outward K(+) current (I(ss)) developed by day 20, and the ultrarapid delayed rectifier K(+) current (I(Kur)) did not fully develop until the mouse reached maturity. Interestingly, the increase in I(Kur) was not associated with a decrease in APD. Comparison of atrial and ventricular K(+) currents showed that I(to) and I(Kur) density were significantly greater in day 7, day 20, and adult myocytes compared with age-matched atrial cells. Overall, it appears that, in mouse ventricle, developmental changes in APD are likely attributable to increases in I(to), I(ss), and I(K1), whereas the role of I(Kur) during postnatal development appears to be less critical to APD.
为了更好地理解未成熟心脏中心脏复极异常的潜在机制，本研究对出生第1天、第7天、第20天的小鼠心室肌细胞以及成年CD1小鼠的钾离子电流进行了表征和比较，以确定出生后发育对心室复极的影响。采用电流钳和膜片钳技术检测分离心肌细胞的动作电位及复极过程中的钾离子电流。运用逆转录聚合酶链反应（RT-PCR）定量检测相关钾离子通道的信使核糖核酸（mRNA）表达。本研究发现，动作电位时程（APD）随年龄增长而缩短，成年心肌细胞的APD最短。本研究还表明，与出生第1天的心肌细胞相比，成年心肌细胞的钾离子电流及各种钾离子通道的mRNA相对丰度显著更高。对总钾离子电流的各个成分进行检测发现，内向整流钾离子电流（I(K1)）在出生第7天时形成，不依赖钙离子的瞬时外向电流（I(to)）和稳态外向钾离子电流（I(ss)）在出生第20天时形成，而超快速延迟整流钾离子电流（I(Kur)）直到小鼠成熟才完全形成。有趣的是，I(Kur)的增加与APD的缩短并无关联。心房和心室钾离子电流的比较显示，与年龄匹配的心房细胞相比，出生第7天、第20天的心肌细胞以及成年心肌细胞的I(to)和I(Kur)密度显著更高。总体而言，在小鼠心室中，APD的发育变化可能归因于I(to)、I(ss)和I(K1)的增加，而I(Kur)在出生后发育过程中对APD的作用似乎不那么关键。
