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

Zhu, Yu and Jerrel L. Yakel. Calcineurin modulates G proteincoupled receptor-mediated inhibition of the N-type Ca mediated inhibition of N-type calcium channels in rat sympathetic channels in rat sympathetic neurons from the male rat major neurons. J. Neurophysiol. 78: 1161–1169, 1997. The modulation pelvic ganglion (MPG) was greatly reduced. The muscarinic of N-type voltage-gated calcium (Ca) channels by G proteinreceptor-induced inhibition of these channels, which does coupled receptors was investigated in sympathetic neurons of the not involve the activation of a GPTX-coupled and membranemale rat major pelvic ganglion (MPG) with the use of whole cell delimited pathway in MPG neurons (Zhu and Yakel 1997) patch-clamp recording techniques from acutely dissociated neuas it does in superior cervical ganglion sympathetic neurons rons. By inhibiting calcineurin, a Ca /calmodulin-regulated (Hille 1994), was unaffected by the inhibition of calprotein phosphatase, the a2 noradrenergic and somatostatin recepcineurin. These data suggest that calcineurin may play an tor-induced inhibition of these N-type Ca channels was greatly reduced. Both of these receptor pathways utilize a pertussis toxinimportant role in regulating neurotransmitter release in symsensitive G protein (GPTX ). The guanosine 5*-o-(3-thiotriphospathetic neurons by reducing presynaptic inhibition, and may phate) (GTPgS)-induced decrease in the amplitude and activation explain why the immunosuppressant drug cyclosporin, a pokinetics of Ca currents, an effect that was similar to the activation tent inhibitor of calcineurin, leads to neurotoxicity and neuof GPTX-coupled receptors, also was reduced by the inhibition of rogenic hypertension. calcineurin. Calcineurin does not regulate the muscarinic receptorinduced inhibition of the N-type Ca channels, a pathway that