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Am J Physiol Cell Physiol 269: C725-C732, 1995;
0363-6143/95 $5.00
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AJP - Cell Physiology, Vol 269, Issue 3 C725-C732, Copyright © 1995 by American Physiological Society


ARTICLES

Voltage-dependent potentiation of neuronal L-type calcium channels due to state-dependent phosphorylation

A. Sculptoreanu, A. Figourov and W. C. De Groat
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.

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.


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