Information Services, Academic Computing Services; Department of Cell Biology; Department of Physiology
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
The Journal of neuroscience : the official journal of the Society for Neuroscience
De Crescenzo V, Fogarty KE, ZhuGe R, Tuft RA, Lifshitz LM, Carmichael J, Bellve KD, Baker SP, Zissimopoulos S, Lai FA, Lemos JR, Walsh JV. (2006). Dihydropyridine receptors and type 1 ryanodine receptors constitute the molecular machinery for voltage-induced Ca2+ release in nerve terminals. Information Technology Publications. https://doi.org/10.1523/JNEUROSCI.1512-06.2006. Retrieved from https://escholarship.umassmed.edu/infoservices/37