Isoform-specific inhibition of voltage-sensitive Ca(2+) channels by protein kinase C in adrenal chromaffin cells.
Selective protein kinase C (PKC) activators and inhibitors were used to investigate the involvement of specific PKC isoforms in the modulation of voltage-sensitive Ca(2+) channels (VSCCs) in bovine adrenal chromaffin cells. Exposure to the phorbol ester phorbol-12,13-dibutyrate (PDBu) inhibited the Ca(2+) currents elicited by depolarizing voltage steps. This inhibition was occluded by the PKC-specific inhibitor Ro 31-8220 but remained unaffected by Gö 6976, a selective inhibitor of conventional PKC isoforms. PDBu treatment caused the translocation of PKC-alpha and -epsilon isoforms from cytosol to membranes. PKC-iota and -zeta showed no signs of translocation. It is concluded that VSCCs are specifically inhibited by the activation of PKC-epsilon in chromaffin cells. This may be relevant to the action of phospholipase-linked receptors involved in the control of Ca(2+) influx, both in catecholaminergic cells and other cell types.
Center for Neuroscience and Cell Biology, University of Combra, Portugal.
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D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D066298:In Vitro Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D015220:Calcium Channels; D010703:Phorbol Esters; D020033:Protein Isoforms; D011493:Protein Kinase C