UMMS Affiliation

Information Services, Academic Computing Services; Department of Cell Biology; Department of Physiology

Publication Date


Document Type



Animals; Calcium; Calcium Channel Agonists; Calcium Channel Blockers; Calcium Channels, L-Type; Cell Membrane; Electric Stimulation; Electrophysiology; Hypothalamus; Immunohistochemistry; Mice; Nerve Endings; Neurons; Nifedipine; Pyrroles; Ryanodine Receptor Calcium Release Channel


Cell and Developmental Biology | Cellular and Molecular Physiology


Ca2+ 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+.

DOI of Published Version



J Neurosci. 2006 Jul 19;26(29):7565-74. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of neuroscience : the official journal of the Society for Neuroscience

Related Resources

Link to article in PubMed

PubMed ID