Pkc-independent inhibition of cardiac l-type ca2+ channel current
by phorbol esters.
Asai, Tatsuya, Lesya M. Shuba, Dieter J. Pelzer, and Terence F.
McDonald.
Department of Physiology and Biophysics, Dalhousie University,
Halifax, Nova Scotia, B3H 4H7 Canada
APStracts 2:0350H, 1995.
Active and inactive phorbol esters were applied to guinea pig
ventricular myocytes to study the responses of L-type Ca2+ (ICa,L)
and L-type Na+ (INa,L) currents. Phorbol 12-myristate 13-acetate
(PMA) (10-100 nM) never stimulated ICa,L or INa,L, and frequently
depressed them by 5-30% in a voltage-independent manner. However, the
phorbol ester consistently activated delayed-rectifying K+ (IK) and
Cl- currents. The inhibition of ICa,L occurred 3 times faster than
co-monitored stimulation of IK, and ICa,L and INa,L were unaffected
by two interventions that suppressed IK stimulation (pretreatment
with 50 [mu]M 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7);
dialysis with pCa 11 versus standard pCa 9 solution). Inactive
phorbol esters 4[alpha]-phorbol 12, 13-didecanoate ([alpha]PDD) and
4[alpha]-phorbol had little effect on IK, but [alpha]PDD had a PMA
-like inhibitory effect on Ca2+ channel currents. We conclude that,
unlike the stimulation of IK by PMA, inhibition of Ca2+ channel
current by phorbol esters is a PKC-independent action.
Received 20 April 1995; accepted in final form 27 July 1995.
APS Manuscript Number H375-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.