RT Journal Article SR Electronic T1 Modulation of High Voltage-Activated Calcium Channels by Somatostatin in Acutely Isolated Rat Amygdaloid Neurons JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6000 OP 6011 DO 10.1523/JNEUROSCI.16-19-06000.1996 VO 16 IS 19 A1 Félix Viana A1 Bertil Hille YR 1996 UL http://www.jneurosci.org/content/16/19/6000.abstract AB We investigated actions of somatostatin (Som) on voltage-gated 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 μm) reduced the peak current by ∼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 ω-conotoxin-GVIA (ω-CgTx) or ω-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 GTPγS led to spontaneous inhibition and a slowing of the current like that with Som and occluded the effects of the peptide. Dialysis with GDPβS also diminished the inhibition. A short preincubation with 50 μm of the alkylating agentN-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.