Protein kinase C participates in up-regulation of dihydropyridine-sensitive calcium channels by ethanol.
Exposure to ethanol for several days increases the expression of dihydropyridine-sensitive, voltage-dependent Ca2+ channels in brain and in the neural cell line PC12. Since protein phosphorylation is a major mechanism by which ion channels are regulated, we used protein kinase inhibitors to investigate whether ethanol-induced up-regulation of Ca2+ channels involves activation of a protein kinase. Sphingosine and polymixin B, which inhibit protein kinase C and calmodulin-dependent kinases, prevented the enhancement of 45Ca2+ uptake induced by exposure of PC12 cells to ethanol for 4 days. In addition, sphingosine blocked the ability of ethanol to increase the number of [3H]dihydropyridine binding sites in PC12 cell membranes. Sphingosine's effect was prevented by simultaneous exposure to phorbol 12,13-dibutyrate, a potent activator of protein kinase C. Therefore, protein kinase C appears to be involved in the up-regulation of dihydropyridine-sensitive Ca2+ channels during prolonged exposure to ethanol.
Messing
R O
RO
Department of Neurology, University of California, San Francisco.
Sneade
A B
AB
Savidge
B
B
D000310:Adrenal Gland Neoplasms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D017275:Isradipine; D007700:Kinetics; D010069:Oxadiazoles / Q000378:metabolism*; D010673:Pheochromocytoma; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013110:Sphingosine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010069:Oxadiazoles; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D011493:Protein Kinase C; D013110:Sphingosine; D011188:Potassium; D002118:Calcium; D017275:Isradipine