CALCINEURIN MODULATES G-PROTEIN-MEDIATED INHIBITION OF N-TYPE CALCIUMCHANNELS IN RAT SYMPATHETIC NEURONS

The modulation of N-type voltage-gated calcium (Ca2+) channels by G pr otein-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 inhib iting calcineurin, a Ca2+/calmodulin-regulated protein phosphatase, th e alpha(2) noradrenergic and somatostatin receptor-induced inhibition of these N-type Ca2+ channels was greatly reduced. Both of these recep tor pathways utilize a pertussis toxin-sensitive G protein (G(PTX)) Th e guanosine 5'-o-(3-thiotriphosphate) (GTP gamma S)-induced decrease i n the amplitude and activation kinetics of Ca2+ currents, an effect th at was similar to the activation of G(PTX)-coupled receptors, also was reduced by the inhibition of calcineurin. Calcineurin does not regula te the muscarinic receptor-induced inhibition of the N-type Ca2+ chann els, 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.