Age-related differences in [beta]-adrenergic regulation of
repolarization in canine epicardial myocytes.
Charpentier, Flavien, Qin-Yue Liu, Michael R. Rosen, and Richard B.
Robinson.
Departments of Pharmacology and Pediatrics, College of Physicians
and Surgeons of Columbia University, New York, NY 10032
APStracts 3:0132H, 1996.
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 further determined the mechanisms of
isoproterenol 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 action potentials 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 pA/pF to 13.43+/-1.92 pA/pF with ISO (step to
+50 mV, P<0.05, n = 6), but 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, 10-7M ISO did increase ICa,L from
172+/-31 pA 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.
Received 12 July 1995; accepted in final form 22 March 1996.
APS Manuscript Number H643-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96