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cAMP-dependent enhancement of dihydropyridine-sensitive calcium channel availability in hippocampal neurons.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 1997 Jul 15; Vol. 17 (14), pp. 5334-48. - Publication Year :
- 1997
-
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-isoquinolinesulfonamide (H-89). Hippocampal neurons contain two kinds of dihydropyridine-sensitive calcium channel activity: Ls and Lp (Kavalali and Plummer, 1994). 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.
Details
- Language :
- English
- ISSN :
- 0270-6474
- Volume :
- 17
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 9204918