AJP - Heart and Circulatory Physiology, Vol 253, Issue 1 205-H209, Copyright © 1987 by American Physiological Society
Effect of phorbol esters on contractile state and calcium flux in cultured chick heart cells
G. F. Leatherman, D. Kim and T. W. Smith
Phorbol esters are potent tumor promoters that have been widely used in
studies of transmembrane signaling because of their ability to activate
protein kinase C. To study the effect of phorbol esters (and indirectly,
the role of protein kinase C) on cardiac muscle contractility, we examined
the effects of phorbol myristate acetate (PMA) on contractile state,
transmembrane 45Ca fluxes, and cytosolic free Ca concentration ([Ca]i)
using spontaneously contracting cultured chick ventricular cells. PMA
produced a concentration- and time-dependent decrease in the amplitude of
cell motion [half maximum inhibitory concentration (IC50) = 130 nM] with
maximal effect (54 +/- 5% of control) observed at 1 microM. PMA (1 microM)
reduced 45Ca uptake rate by 16 +/- 4% (P less than 0.05) and the size of
the rapidly exchangeable Ca pool by 11 +/- 2% (P less than 0.05) but did
not alter the 45Ca efflux rate. In fura-2-loaded cells, PMA produced a
decrease in [Ca]i from 96 +/- 7 to 72 +/- 5 nM (mean +/- SE; P less than
0.05) with a time course similar to that of alteration in contractile
amplitude. PMA had no effect on cellular Na content. Phorbol didecanoate (1
microM), a phorbol diester that does not activate protein kinase C,
produced no significant changes in contractile amplitude, 45Ca fluxes, or
[Ca]i. These results indicate that PMA influences transsarcolemmal Ca
uptake, and thus the excitation-contraction process, and suggest that
protein kinase C may modulate myocardial Ca homeostasis and contractile
state.
