cAMP-dependent enhancement of dihydropyridine-sensitive calcium channel availability in hippocampal neurons

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

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Abstract

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 McDonald et al., 1994) and has been suggested to be essential for voltage-dependent facilitation in adrenal chromaffin cells (Artalejo et al., 1992) and skeletal muscle (Sculptoreanu et al., 1993b). 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-isoquinoline-sulfonamide (H-89). Hippocampal neurons contain two kinds of dihydropyridine-sensitive calcium channel activity: Ls and Lp (Kavalali and Plummer, 1994). The L(s channel closely resembles the cardiac L-type channel, whereas the Lp channel shows a novel low-voltage form of voltage-dependent potentiation (Kavalali and Plummer, 1996). 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.

Original languageEnglish (US)
Pages (from-to)5334-5348
Number of pages15
JournalJournal of Neuroscience
Volume17
Issue number14
StatePublished - Jul 30 1997

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Keywords

  • Calcium channel
  • Dihydropyridine
  • Facilitation
  • H-7
  • H-89
  • Hippocampus
  • Phosphorylation
  • Potentiation
  • Protein kinase A
  • cAMP

ASJC Scopus subject areas

  • Neuroscience(all)

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