Modulation of high voltage-activated calcium channels by somatostatin in acutely isolated rat amygdaloid neurons.
We investigated actions of somatostatin (Som) on voltagegated calcium channels in acutely isolated rat amygdaloid neurons. Somatostatin caused a dose-dependent inhibition of the high voltage-activated (HVA) Ca2+ current, with little or no effect on the low voltage-activated (LVA) current. Nifedipine (2-10 microM) reduced the peak current by approximately 15% without reducing inhibition of current by Som significantly, ruling out L-type channels as the target of modulation. The modulation appears to involve N- and P/Q-type calcium channels. After pretreatment with omega-conotoxin-GVIA (omega-CgTx) or omega-agatoxin-IVA, the inhibition was reduced but not abolished, whereas the combined application of both toxins nearly abolished the modulation. The Som analog BIM-23060 mimicked the effects of Som, whereas BIM-23058 had no effect, implicating Som type-2 receptors (SSTR-2). The inhibition was voltage-dependent, being minimal for small depolarizations, and was often accompanied by a slowing of the activation time course. Strong depolarizing prepulses partially relieved the inhibition and restored the time course of activation. Intracellular dialysis with GTP gamma S led to spontaneous inhibition and a slowing of the current like that with Som and occluded the effects of the peptide. Dialysis with GDP beta S also diminished the inhibition. A short preincubation with 50 microM of the alkylating agent N-ethylmaleimide (NEM) prevented the action of somatostatin. These results suggest a role for NEM-sensitive G-proteins in the Som inhibition. Application of 8-CPT-cAMP and IBMX did not mimic or prevent the effects of Som.
Viana
F
F
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195-7290, USA.
Hille
B
B
D000679:Amygdala / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D002469:Cell Separation; D000242:Cyclic AMP / Q000502:physiology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017481:Receptors, Somatostatin; D013004:Somatostatin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins