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Volume 17, Number 14, Issue of July 15, 1997 pp. 5334-5348
Copyright ©1997 Society for Neuroscience

cAMP-Dependent Enhancement of Dihydropyridine-Sensitive Calcium Channel Availability in Hippocampal Neurons

Received Jan. 24, 1997; revised May 5, 1997; accepted May 7, 1997.

Ege T. Kavalali, Katherine S. Hwang, and Mark R. Plummer

Department of Biological Sciences, Rutgers University, Piscataway, New Jersey 08855-1059

Dihydropyridine-sensitive calcium channels can be strongly modulated by cAMP-dependent phosphorylation. This modulation takes the form of increased channel availability in cardiac myocytes (for review, see ) and has been suggested to be essential for voltage-dependent facilitation in adrenal chromaffin cells () and skeletal muscle (). To determine the role of cAMP-dependent phosphorylation on dihydropyridine-sensitive calcium channels in hippocampal neurons, we have used both single-channel and whole-cell recording techniques and have examined the effects of the membrane-permeable cAMP analog 8-(4-chlorophenylthio) (CPT)-cAMP and the protein kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and N-[2-(p-bromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide (H-89).

Hippocampal neurons contain two kinds of dihydropyridine-sensitive calcium channel activity: Ls and Lp (). The Ls channel closely resembles the cardiac L-type channel, whereas the Lp channel shows a novel low-voltage form of voltage-dependent potentiation (). 8-CPT-cAMP increased the availability of both the Ls and Lp channels and caused a parallel increase in Lp channel reopenings at the repolarization potential that result from voltage-dependent potentiation. This effect was completely blocked by the broad spectrum kinase inhibitor H-7 and by the protein kinase A-specific inhibitor H-89. The two inhibitors, however, did not disrupt baseline potentiation of the Lp channel, suggesting that cAMP-dependent protein kinase activity can enhance Ls and Lp channel activity but is not required for voltage-dependent potentiation in hippocampal neurons.

Key words: calcium channel; hippocampus; potentiation; phosphorylation; facilitation; dihydropyridine; cAMP; protein kinase A; H-7; H-89




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