De Crescenzo, ValerieFogarty, Kevin E.ZhuGe, RonghuaTuft, Richard A.Lifshitz, Lawrence M.Carmichael, JeffreyBellve, Karl D.Baker, Stephen P.Zissimopoulos, SpyrosLai, F. AnthonyLemos, Jose R.Walsh, John V. Jr.2022-08-232022-08-232006-07-212008-05-05J Neurosci. 2006 Jul 19;26(29):7565-74. <a href="http://dx.doi.org/10.1523/JNEUROSCI.1512-06.2006">Link to article on publisher's site</a>1529-2401 (Electronic)10.1523/JNEUROSCI.1512-06.200616855084https://hdl.handle.net/20.500.14038/35292Ca2+ stores were studied in a preparation of freshly dissociated terminals from hypothalamic magnocellular neurons. Depolarization from a holding level of -80 mV in the absence of extracellular Ca2+ elicited Ca2+ release from intraterminal stores, a ryanodine-sensitive process designated as voltage-induced Ca2+ release (VICaR). The release took one of two forms: an increase in the frequency but not the quantal size of Ca2+ syntillas, which are brief, focal Ca2+ transients, or an increase in global [Ca2+]. The present study provides evidence that the sensors of membrane potential for VICaR are dihydropyridine receptors (DHPRs). First, over the range of -80 to -60 mV, in which there was no detectable voltage-gated inward Ca2+ current, syntilla frequency was increased e-fold per 8.4 mV of depolarization, a value consistent with the voltage sensitivity of DHPR-mediated VICaR in skeletal muscle. Second, VICaR was blocked by the dihydropyridine antagonist nifedipine, which immobilizes the gating charge of DHPRs but not by Cd2+ or FPL 64176 (methyl 2,5 dimethyl-4[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate), a non-dihydropyridine agonist specific for L-type Ca2+ channels, having no effect on gating charge movement. At 0 mV, the IC50 for nifedipine blockade of VICaR in the form of syntillas was 214 nM in the absence of extracellular Ca2+. Third, type 1 ryanodine receptors, the type to which DHPRs are coupled in skeletal muscle, were detected immunohistochemically at the plasma membrane of the terminals. VICaR may constitute a new link between neuronal activity, as signaled by depolarization, and a rise in intraterminal Ca2+.en-USAnimalsCalciumCalcium Channel AgonistsCalcium Channel BlockersCalcium Channels, L-TypeCell MembraneElectric StimulationElectrophysiologyHypothalamusImmunohistochemistryMiceNerve EndingsNeuronsNifedipinePyrrolesRyanodine Receptor Calcium Release ChannelCell and Developmental BiologyCellular and Molecular PhysiologyJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1036&amp;context=infoservices&amp;unstamped=1https://escholarship.umassmed.edu/infoservices/37503918infoservices/37