Ventricular action potential adaptation to regular exercise: role of β-adrenergic and K_ATP channel function

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_ATP) 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. Ca²⁺ transient durations reflected the changes in APD, while Ca²⁺ 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 β₁-AR blocker atenolol, but not the β₂-AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β₁-AR. At 10 Hz, the K_ATP 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 β₁-AR responsiveness and K_ATP 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 Ca²⁺ influx; during exercise, an increase in K_ATP channel activity would shorten APD and, thus, protect the heart against Ca²⁺ overload or inadequate filling.NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca²⁺ 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 β₁-adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher K_ATP channel function.