AJP - Heart and Circulatory Physiology, Vol 266, Issue 4 1551-H1557, Copyright © 1994 by American Physiological Society
Differential modulation by adenylate cyclase of Ca2+ and delayed K+ current in ventricular myocytes
K. Harada and T. Iijima
Department of Pharmacology, Akita University School of Medicine, Japan.
This study was designed to investigate the differential modulation of the
L-type Ca2+ (ICa) and the delayed rectifier K+ (IK) currents by direct
activation of adenylate cyclase in guinea pig ventricular preparations.
Action potentials were measured with conventional microelectrodes in
excised papillary muscles. Isoproterenol significantly shortened the action
potential duration at 90% repolarization (APD90) at 0.1 nM but
significantly prolonged it at a higher concentration (10 nM). A
water-soluble forskolin derivative, 6-(3-dimethylaminopropionyl) forskolin
(NKH-477), slightly but significantly shortened APD at 12 nM but not at a
higher concentration (120 nM). Effects of isoproterenol and NKH-477 on ICa
and IK were also investigated by use of the whole cell voltage-clamp
technique in single ventricular cells. Isoproterenol increased not only IK
but also ICa at the same threshold concentration (0.3 nM). In contrast, the
threshold concentration of NKH-477 for increasing IK (approximately 1 nM)
was clearly lower than that for increasing ICa (10 nM). These results
indicate that ICa and IK channels could be differentially regulated during
beta-adrenoceptor stimulation.
