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- Title
Dihydropyridine Receptors and Type 1 Ryanodine Receptors Constitute the Molecular Machinery for Voltage-Induced Ca<sup>2+</sup> Release in Nerve Terminals.
- Authors
De Crescenzo, Valérie; Fogarty, Kevin E.; ZhuGe, Ronghua; Tuft, Richard A.; Lifshitz, Lawrence M.; Carmichael, Jeffrey; Bellvé, Karl D.; Baker, Stephen P.; Zissimopoulos, S.; Lai, F. Anthony; Lemos, José R.; Walsh Jr., John V.
- Abstract
Ca2+ stores were studied in a preparation of freshly dissociated terminals from hypothalamic magnocellular neurons. Depolarizationfroma holding level of--80m V in the absence of extracellular Ca2+ elicited Ca2+ release from intraterminal stores, aryanodine-sensitive process designated as voltage-induced Ca2+ release (VICaR). There lease 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 8.4m V 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 FPL64176 (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. At0mV, 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+.
- Subjects
NEURONS; DIHYDROPYRIDINE; NERVOUS system; CELL membranes; NIFEDIPINE
- Publication
Journal of Neuroscience, 2006, Vol 26, Issue 29, p4
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1512-06.2006