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 1 and voltage dependence 2 of these channels are controlled by a membrane-associated pathway involv-ing 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 inhibi-tion of Ca 2+ 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 Ca 2+ 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 soma-tostatin induces a sustained inhibition of neuronal calcium channels.