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dc.contributor.authorDe Crescenzo, Valerie
dc.contributor.authorFogarty, Kevin E.
dc.contributor.authorZhuGe, Ronghua
dc.contributor.authorTuft, Richard A.
dc.contributor.authorLifshitz, Lawrence M.
dc.contributor.authorCarmichael, Jeffrey
dc.contributor.authorBellve, Karl D.
dc.contributor.authorBaker, Stephen P.
dc.contributor.authorZissimopoulos, Spyros
dc.contributor.authorLai, F. Anthony
dc.contributor.authorLemos, Jose R.
dc.contributor.authorWalsh, John V. Jr.
dc.date2022-08-11T08:09:11.000
dc.date.accessioned2022-08-23T16:20:29Z
dc.date.available2022-08-23T16:20:29Z
dc.date.issued2006-07-21
dc.date.submitted2008-05-05
dc.identifier.citationJ 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>
dc.identifier.issn1529-2401 (Electronic)
dc.identifier.doi10.1523/JNEUROSCI.1512-06.2006
dc.identifier.pmid16855084
dc.identifier.urihttp://hdl.handle.net/20.500.14038/35292
dc.description.abstractCa2+ 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+.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16855084&dopt=Abstract ">Link to article in PubMed</a>
dc.subjectAnimals
dc.subjectCalcium
dc.subjectCalcium Channel Agonists
dc.subjectCalcium Channel Blockers
dc.subjectCalcium Channels, L-Type
dc.subjectCell Membrane
dc.subjectElectric Stimulation
dc.subjectElectrophysiology
dc.subjectHypothalamus
dc.subjectImmunohistochemistry
dc.subjectMice
dc.subjectNerve Endings
dc.subjectNeurons
dc.subjectNifedipine
dc.subjectPyrroles
dc.subjectRyanodine Receptor Calcium Release Channel
dc.subjectCell and Developmental Biology
dc.subjectCellular and Molecular Physiology
dc.titleDihydropyridine receptors and type 1 ryanodine receptors constitute the molecular machinery for voltage-induced Ca2+ release in nerve terminals
dc.typeJournal Article
dc.source.journaltitleThe Journal of neuroscience : the official journal of the Society for Neuroscience
dc.source.volume26
dc.source.issue29
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1036&amp;context=infoservices&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infoservices/37
dc.identifier.contextkey503918
refterms.dateFOA2022-08-23T16:20:29Z
html.description.abstract<p>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+.</p>
dc.identifier.submissionpathinfoservices/37
dc.contributor.departmentDepartment of Physiology
dc.contributor.departmentDepartment of Cell Biology
dc.contributor.departmentInformation Services, Academic Computing Services
dc.source.pages7565-74


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