Somatostatin-induced inhibition of neuronal Ca2+ current modulated by cGMP-dependent protein kinase.
Neurotransmitter release is frequently regulated by peptides that modulate neuronal calcium channels. Whole-cell recordings show that the ion permeability and voltage dependence of these channels are controlled by a membrane-associated pathway involving GTP-binding proteins. Here we use perforated-patch recordings to show that, in addition to this pathway, the peptide somatostatin inhibits the calcium current in chick ciliary ganglion neurons by a second soluble pathway involving a cyclic GMP-dependent protein kinase (cGMP-PK). This somatostatin inhibition of Ca2+ current did not desensitize and was not characterized by the slowing of Ca(2+)-current activation (kinetic slowing) observed in whole-cell recordings. When cGMP-PK was inhibited, somatostatin inhibition of Ca2+ current resembled that observed with whole-cell recordings. cGMP agonists mimic the effect of somatostatin only in perforated patch recordings. An endogenous cGMP-PK therefore forms part of the mechanism by which somatostatin induces a sustained inhibition of neuronal calcium channels.
Meriney
S D
SD
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269.
Gray
D B
DB
Pilar
G R
GR
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D002645:Chickens; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D005726:Ganglia, Parasympathetic / Q000166:cytology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D013004:Somatostatin / Q000502:physiology*
D015220:Calcium Channels; D013004:Somatostatin; D017869:Cyclic GMP-Dependent Protein Kinases