@article {Viana6000, author = {F{\'e}lix Viana and Bertil Hille}, title = {Modulation of High Voltage-Activated Calcium Channels by Somatostatin in Acutely Isolated Rat Amygdaloid Neurons}, volume = {16}, number = {19}, pages = {6000--6011}, year = {1996}, doi = {10.1523/JNEUROSCI.16-19-06000.1996}, publisher = {Society for Neuroscience}, abstract = {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{\textendash}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.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/16/19/6000}, eprint = {https://www.jneurosci.org/content/16/19/6000.full.pdf}, journal = {Journal of Neuroscience} }