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Protein Kinase C Participates in Up‐Regulation of Dihydropyridine‐Sensitive Calcium Channels by Ethanol
Author(s) -
Messing Robert O.,
Sneade Alisa B.,
Savidge Beth
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb03150.x
Subject(s) - protein kinase c , sphingosine , dihydropyridine , protein kinase a , activator (genetics) , kinase , chemistry , microbiology and biotechnology , voltage dependent calcium channel , calmodulin , biochemistry , calcium , biology , enzyme , receptor , organic chemistry
Exposure to ethanol for several days increases the expression of dihydropyridine‐sensitive, voltage‐dependent Ca 2+ 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 Ca 2+ channels involves activation of a protein kinase. Sphingosine and polymixin B, which inhibit protein kinase C and calmodulin‐dependent kinases, prevented the enhancement of 45 Ca 2+ 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 [ 3 H]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 Ca 2+ channels during prolonged exposure to ethanol.