Wang Xinrui, Fitts Robert H
Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin.
Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin
J Appl Physiol (1985). 2017 Aug 1;123(2):285-296. doi: 10.1152/japplphysiol.00197.2017. Epub 2017 May 18.
Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K (K) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca transient durations reflected the changes in APD, while Ca transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β-AR blocker atenolol, but not the β-AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β-AR. At 10 Hz, the K channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β-AR responsiveness and K channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca influx; during exercise, an increase in K channel activity would shorten APD and, thus, protect the heart against Ca overload or inadequate filling. Our data demonstrated that regular exercise prolonged the action potential and Ca transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic receptor agonist dose-response curve rightward compared with controls by reducing β-adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher K channel function.
众所周知，规律的运动训练会影响动作电位时程（APD）并改善心脏功能，但β-肾上腺素能受体（β-AR）亚型和/或ATP敏感性钾（K）通道是否参与其中尚不清楚。为了解决这个问题，将雌性和雄性Sprague-Dawley大鼠随机分为自愿轮转运动组或对照组；训练6-8周后将它们麻醉，并分离出心肌细胞。运动训练显著增加了1 Hz时心尖和心底心肌细胞的APD，并缩短了10 Hz时的APD。钙瞬变持续时间反映了APD的变化，而钙瞬变幅度不受轮转运动的影响。非选择性β-AR激动剂异丙肾上腺素缩短了心肌细胞APD，而轮转运动减弱了这种作用。异丙肾上腺素诱导的APD缩短在很大程度上被选择性β-AR阻滞剂阿替洛尔逆转，但未被β-AR阻滞剂ICI 118,551逆转，这表明轮转运动降低了β-AR的敏感性。在10 Hz时，K通道抑制剂格列本脲在运动训练的大鼠中比对照组更能延长心肌细胞APD，这表明该通道在运动诱导的10 Hz时APD缩短中起作用。这项研究的一个新发现是，β-AR反应性改变和K通道功能在训练诱导的APD调节中具有双重重要性。对跳动的心脏具有生理重要性的是，对肾上腺素能激动剂反应的降低会通过延长APD和钙内流来增强静息心率下的心脏收缩力，此时交感神经驱动较低；在运动期间，K通道活性的增加会缩短APD，从而保护心脏免受钙超载或充盈不足的影响。我们的数据表明，规律运动延长了从心尖和心底区域分离的心肌细胞在1 Hz时的动作电位和钙瞬变持续时间，并在10 Hz刺激时缩短了两者。新发现是，与对照组相比，轮转运动通过降低β-肾上腺素能受体反应性使β-肾上腺素能受体激动剂剂量反应曲线向右移动，并且在高激活率下，来自训练动物的心肌细胞表现出更高的K通道功能。
