The Journal of Neurophysiology Vol. 78 No. 2 August 1997, pp. 1161-1169
Copyright ©1997 The American Physiological Society

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Calcineurin Modulates G Protein-Mediated Inhibition of N-Type Calcium Channels in Rat Sympathetic Neurons

Yu Zhu and Jerrel L. Yakel

Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Zhu, Yu and Jerrel L. Yakel. Calcineurin modulates G protein-mediated inhibition of N-type calcium channels in rat sympathetic neurons. J. Neurophysiol. 78: 1161-1169, 1997. The modulation of N-type voltage-gated calcium (Ca²⁺) channels by G protein-coupled receptors was investigated in sympathetic neurons of the male rat major pelvic ganglion (MPG) with the use of whole cell patch-clamp recording techniques from acutely dissociated neurons. By inhibiting calcineurin, a Ca²⁺/calmodulin-regulatedprotein phosphatase, the ₂ noradrenergic and somatostatin receptor-induced inhibition of these N-type Ca²⁺ channels was greatly reduced. Both of these receptor pathways utilize a pertussis toxin-sensitive G protein (G_PTX). The guanosine 5-o-(3-thiotriphosphate) (GTPS)-induced decrease in the amplitude and activation kinetics of Ca²⁺ currents, an effect that was similar to the activation of G_PTX-coupled receptors, also was reduced by the inhibition of calcineurin. Calcineurin does not regulate the muscarinic receptor-induced inhibition of the N-type Ca²⁺ channels, a pathway that utilizes a different G protein in the MPG neurons. Thus calcineurin appears to selectively regulate the coupling between the G_PTX and the Ca²⁺ channel.

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