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

• Published in: The American journal of physiology Vol. 269; no. 3 Pt 1; p. C725
• Main Authors: Sculptoreanu, A, Figourov, A, De Groat, W C
• Format: Journal Article
• Language: English
• Published: United States 01.09.1995
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Calcium Channels - physiology; Cells, Cultured; Conditioning (Psychology); Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Down-Regulation; Electric Stimulation; Electrophysiology; Enzyme Activation; Ganglia - cytology; Ganglia, Spinal - cytology; Isradipine - pharmacology; Male; Neurons - drug effects; Neurons - metabolism; Pelvis - innervation; Phosphorylation; Rats
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1995.269.3.c725

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.