Effects of regular exercise on ventricular myocyte biomechanics and KATP channel function

Abstract

Exercise training is known to protect the heart from ischemia and improve function during exercise by reducing cardiomyocyte action potential duration (APD) and increasing contractility. The cellular mechanisms involve β-adrenergic regulation and the ATP-sensitive K+ (KATP) channel, but how each alters function of the left ventricle and sex specificity is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to wheel-running (TRN) or sedentary (SED) groups. After 6–8 wk of training, myocytes were isolated from the left ventricle and field stimulated at 1, 2, and 5 Hz. TRN significantly increased cardiomyocyte contractility, the kinetics of the Ca2+ transient, and responsiveness to the adrenergic receptor agonist isoproterenol (ISO), as reflected by an increased sarcomere shortening. Importantly, we demonstrated a TRN-induced upregulation of KATP channels, which was reflected by elevated content, current density, and the channel’s contribution to APD shortening at high activation rates and in the presence of the activator pinacidil. TRN induced increase in KATP current occurred throughout the left ventricle, but channel subunit content showed regional specificity with increases in Kir6.2 in the apex and SUR2A in base regions. In summary, TRN elevated cardiomyocyte cross-bridge kinetics, Ca2+ sensitivity, and the responsiveness of contractile function to β-adrenergic receptor stimulation in both sexes. Importantly, upregulation of the KATP channel accelerates repolarization and shortens APD during stress and exercise. These adaptations have clinical importance, as increased contractility and reduced APD would help protect cardiac output and reduce intracellular Ca2+ overload during stresses such as regional ischemia. NEW & NOTEWORTHY Our results demonstrate that regular exercise significantly increased ventricular myocyte shortening and relaxation velocity and the rate of rise in intracellular Ca2+ transient and enhanced the response of biomechanics and Ca2+ reuptake to β-adrenergic stimulation. Importantly, exercise training upregulated the cardiomyocyte sarcolemma ATP-sensitive K+ channel across the left ventricle in both sexes, as reflected by elevated channel subunit content, current density, and the channel’s contribution to reduced action potential duration at high activation rates.