Stones Rachel, Billeter Rudolf, Zhang Henggui, Harrison Simon, White Ed
Institute of Membrane and Systems Biology and Multidisciplinary Cardiovascular Research Centre, University of Leeds, Garstang Building, Leeds LS29JT, UK.
Basic Res Cardiol. 2009 Nov;104(6):643-52. doi: 10.1007/s00395-009-0030-6. Epub 2009 May 5.
Regular exercise can lead to electrical remodelling of the heart. The cellular mechanisms associated with these changes are not well understood, and are difficult to study in human tissue but are important given that exercise is recommended to the general population. We have investigated the role played by the transient outward K+ current (I(to)) in the changes in electrical activity seen in response to voluntary exercise training in rats. Female rats undertook 6 weeks of voluntary wheel running exercise (TRN) or were sedentary controls (SED). Monophasic action potentials (MAPs) were recorded from the surface of whole hearts. Whole cell patch clamp recordings of I(to); mRNA and protein levels of selected targets in sub-epicardial (EPI) and sub-endocardial myocardium of SED and TRN hearts were compared. In TRN rats, heart weight:body weight was significantly increased and epicardial MAPs significantly prolonged. I(to) density was reduced in TRN EPI myocytes, such that the transmural gradient of I(to) was significantly reduced (P < 0.05). Computer modelling of these changes in I(to) predicted the observed changes in action potential profile. However, transmural gradients in mRNA and protein expression for Kv4.2 or mRNA levels of the Kv4.2 regulators; KChIP2 and Irx-5 were not significantly altered by voluntary exercise. We conclude that voluntary exercise electrical remodelling is caused, at least in part, by a decrease in EPI I(to), possibly because of fewer functional channels in the membrane, which results in a fall in the transmural action potential duration gradient.
规律运动可导致心脏电重构。与这些变化相关的细胞机制尚未完全明确，且在人体组织中难以研究，但鉴于运动对普通人群有益，所以这些机制很重要。我们研究了瞬时外向钾电流（I(to)）在大鼠自愿运动训练后心脏电活动变化中所起的作用。雌性大鼠进行了6周的自愿轮转跑步运动（TRN），或作为久坐对照组（SED）。从完整心脏表面记录单相动作电位（MAPs）。对I(to)进行全细胞膜片钳记录；比较SED组和TRN组心脏心外膜（EPI）和心内膜下心肌中选定靶点的mRNA和蛋白质水平。在TRN组大鼠中，心脏重量与体重之比显著增加，心外膜MAPs显著延长。TRN组EPI心肌细胞中I(to)密度降低，使得I(to)的跨壁梯度显著降低（P < 0.05）。对I(to)这些变化进行计算机模拟，预测了动作电位波形的观察变化。然而，Kv4.2的mRNA和蛋白质表达的跨壁梯度或Kv4.2调节因子KChIP2和Irx - 5的mRNA水平并未因自愿运动而发生显著改变。我们得出结论，自愿运动引起的心脏电重构至少部分是由EPI中I(to)的减少所致，可能是由于膜上功能性通道减少，从而导致跨壁动作电位时程梯度下降。
