Age-related differences in beta-adrenergic regulation of repolarization in canine epicardial myocytes

Abstract

Developmental changes occur in beta-adrenergic modulation of repolarization in canine. Purkinje fibers that may have important implications for rhythm and arrhythmias. No comparable data exist for ventricular myocardium. Therefore, we studied developmental changes in beta-adrenergic regulation of repolarization and delayed rectifier potassium current (IK) in canine ventricular epicardium. We first investigated the effects of isoproterenol (Iso) on action potentials (AP) recorded from epicardial slices with standard microelectrodes, and then we further determined the mechanisms of Iso action using the nystatin-perforated patch technique on isolated epicardial myocytes. In microelectrode studies Iso (10(-7) M) induced a shortening of the AP in preparations from adult dogs but not in those from dogs < 30 days old. These results were confirmed on AP recorded from single myocytes. Although the plateau was increased by Iso at all ages, the AP at 90% of repolarization was shortened (P < 0.05, n = 6) in adult but unchanged in < 30-day-old myocytes (NS, n = 6). Voltage-clamp studies showed that IK of adult cells was increased from a control value of 10.23 +/- 1.87 to 13.43 +/- 1.92 pA/pF with Iso (step to +50 mV, P < 0.05, n = 6), but IK was not modified in cells from young animals (6.49 +/- 2.72 pA/pF in control and 6.56 +/- 2.62 pA/pF with Iso, n = 4). Increasing the Iso concentration to 10(-5) M failed to increase IK significantly (n = 4). However, 10(-7) M Iso did increase L-type Ca2+ current from 172 +/- 31 to 262 +/- 42 pA (P < 0.05, n = 4), consistent with the effect to increase the AP plateau. These results show that there are developmental changes in beta-adrenergic regulation of repolarization in canine epicardium and that the control site of developmental changes is in the IK channel rather than the beta-adrenergic receptor cascade.