1,2-dioctanoyl-sn-glycerol depresses cardiac l-type ca2+ current
independent of protein kinase c activation.
Schreur, Kevin D., and Shi Liu.
Department of Pharmacology and Toxicology and Department of
Medicine, Division of Cardiology, University of Arkansas for Medical
Sciences, Little Rock, AR 72205
APStracts 2:0332C, 1995.
The present study examines the effect of 1,2-dioctanoyl-sn-glycerol
(DiC8), a diacylglycerol, on L-type Ca2+ current (ICa,L) in adult rat
ventricular myocytes using whole-cell patch-clamp techniques.
Extracellular application of DiC8 (1-10 M) resulted in a
concentration-dependent inhibition of peak ICa,L (EC50 = 2.2 M).
Results obtained from the current-voltage relationship showed that
DiC8 decreased the slope conductance. In addition, DiC8 increased the
rate of IBa inactivation and caused a hyperpolarizing shift in the
steady-state inactivation by 6 mV and a decrease in the slope factor.
The DiC8-induced inhibition of ICa,L was neither mimicked by
activation of PKC with 100 nM phorbol myristate acetate (PMA) nor
prevented by inhibition of PKC with 30 M H7, 100 nM staurosporine or
24 hr pretreatment with PMA. These results suggest that in rat
ventricular myocytes, 1) DAG inhibits ICa,L possibly by facilitating
channel inactivation and decreasing channel availability. and 2) that
this inhibitory effect of DAG is independent of PKC activation.
Received 26 May 1995; accepted in final form 31 August 1995.
APS Manuscript Number C308-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.