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Title: Effect of phorbol esters on contractile state and calcium flux in cultured chick heart cells

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:6395562

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 the cardiac muscle contractility, the authors examined the effects of phorbol myristate acetate (PMA) on contractile state, transmembrane /sup 45/Ca fluxes, and cytosolic free Ca concentration ((Ca)/sub 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) with maximal effect observed at 1 ..mu..M. PMA (1 ..mu..M) reduced /sup 45/Ca uptake rate by 16 /plus minus/ 4% and the size of the rapidly exchangeable Ca pool by 11 /plus minus/ 2%, but did not alter the /sup 45/Ca efflux rate. In fura-2-loaded cells. PMA produced a decrease in (Ca)/sub i/ from 96 /plus minus/ 7 to 72 /plus minus/ 5 nM with a time course similar to that of alteration in contractile amplitude. 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 homeostassis and contractile state.

Research Organization:
Brigham and Women's Hospital, Boston, MA (USA)
OSTI ID:
6395562
Journal Information:
Am. J. Physiol.; (United States), Vol. 253:1
Country of Publication:
United States
Language:
English

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