Voltage-dependent potentiation of neuronal L-type calcium channels due to state-dependent phosphorylation.
Modulation of Ca2+ channels during repetitive activity in excitable cells can have an important role in altering cellular function. In mammalian parasympathetic and dorsal root ganglion neurons, L-type Ca2+ channels are potentiated by single depolarizing prepulses or trains of short high-frequency depolarizing pulses. This type of potentiation takes place regardless of whether Ca2+ or Ba2+ is the charge carrier and requires phosphorylation by a adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. The magnitude of facilitation was correlated with frequency of conditioning trains, was enhanced by 8-bromoadenosine 3',5'-cyclic monophosphate or the Sp diastereomer of adenosine 3',5'-cyclic monophosphothioate (cAMPS), and reduced by Rp-cAMPS or a peptide inhibitor of cAMP-dependent protein kinase. The N-type Ca2+ channels exhibited the opposite response to these agents. We propose that the potentiation of L-type Ca2+ channel currents in neurons is due to state-dependent phosphorylation by cAMP-dependent protein kinase (Sculptoreanu, A., T. Scheuer, and W. A. Catterall. Nature Lond. 364: 240-243, 1993; Sculptoreanu, A., E. Rotman, M. Takahashi, T. Scheuer, and W. A. Catterall. Proc. Natl. Acad. Sci. USA 90: 10135-10139, 1993.). Thus state-dependent phosphorylation in neurons may be a mechanism for the regulation of various functions including transmitter release.
Sculptoreanu
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Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
Figourov
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De Groat
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WC
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D003213:Conditioning, Psychological; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation; D004558:Electric Stimulation; D004594:Electrophysiology; D004789:Enzyme Activation; D005724:Ganglia / Q000166:cytology; D005727:Ganglia, Spinal / Q000166:cytology; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010388:Pelvis / Q000294:innervation; D010766:Phosphorylation; D051381:Rats
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D017275:Isradipine