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.
Zhu
Y
Y
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Yakel
J L
JL
D000818:Animals; D019703:Calcineurin; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002148:Calmodulin-Binding Proteins / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*
D002121:Calcium Channel Blockers; D002148:Calmodulin-Binding Proteins; D018721:Muscarinic Agonists; D018377:Neurotransmitter Agents; D013004:Somatostatin; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins