TY - JOUR T1 - Dihydropyridine Receptors and Type 1 Ryanodine Receptors Constitute the Molecular Machinery for Voltage-Induced Ca<sup>2+</sup> Release in Nerve Terminals JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7565 LP - 7574 DO - 10.1523/JNEUROSCI.1512-06.2006 VL - 26 IS - 29 AU - Valérie De Crescenzo AU - Kevin E. Fogarty AU - Ronghua ZhuGe AU - Richard A. Tuft AU - Lawrence M. Lifshitz AU - Jeffrey Carmichael AU - Karl D. Bellvé AU - Stephen P. Baker AU - S. Zissimopoulos AU - F. Anthony Lai AU - José R. Lemos AU - John V. Walsh, Jr Y1 - 2006/07/19 UR - http://www.jneurosci.org/content/26/29/7565.abstract N2 - 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+. ER -