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

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-regulated protein phosphatase, the alpha2 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) (GTPgammaS)-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.