File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Graded recruitment and inactivation of single InsP3 receptor Ca2+-release channels: Implications for quartal Ca2+release

TitleGraded recruitment and inactivation of single InsP3 receptor Ca2+-release channels: Implications for quartal Ca2+release
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2006
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0022-3751
Citation
Journal Of Physiology, 2006, v. 573 n. 3, p. 645-662 How to Cite?
AbstractModulation of cytoplasmic free Ca2+ concentration ([Ca2+]i) by receptor-mediated generation of inositol 1,4,5-trisphosphate (InsP3) and activation of its receptor (InsP3R), a Ca2+-release channel in the endoplasmic reticulum, is a ubiquitous signalling mechanism. A fundamental aspect of InsP3-mediated signalling is the graded release of Ca2+ in response to incremental levels of stimuli. Ca2+ release has a transient fast phase, whose rate is proportional to [InsP3], followed by a much slower one even in constant [InsP3]. Many schemes have been proposed to account for quantal Ca2+ release, including the presence of heterogeneous channels and Ca2+ stores with various mechanisms of release termination. Here, we demonstrate that mechanisms intrinsic to the single InsP3R channel can account for quantal Ca2+ release. Patch-clamp electrophysiology of isolated insect Sf9 cell nuclei revealed a consistent and high probability of detecting functional endogenous InsP3R channels, enabling InsP3-induced channel inactivation to be identified as an inevitable consequence of activation, and allowing the average number of activated channels in the membrane patch (NA) to be accurately quantified. InsP3-activated channels invariably inactivated, with average duration of channel activity reduced by high [Ca2+]i and suboptimal [InsP3]. Unexpectedly, NA was found to be a graded function of both [Ca2+]i and [InsP3]. A qualitative model involving Ca2+-induced InsP3R sequestration and inactivation can account for these observations. These results suggest that apparent heterogeneous ligand sensitivity can be generated in a homogeneous population of InsP3R channels, providing a mechanism for graded Ca2+ release that is intrinsic to the InsP3R Ca2+ release channel itself. © 2006 The Authors. Journal compilation © 2006 The Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/132540
ISSN
2015 Impact Factor: 4.731
2015 SCImago Journal Rankings: 2.670
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorIonescu, Len_HK
dc.contributor.authorCheung, KHen_HK
dc.contributor.authorVais, Hen_HK
dc.contributor.authorMak, DODen_HK
dc.contributor.authorWhite, Cen_HK
dc.contributor.authorFoskett, JKen_HK
dc.date.accessioned2011-03-28T09:26:06Z-
dc.date.available2011-03-28T09:26:06Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Physiology, 2006, v. 573 n. 3, p. 645-662en_HK
dc.identifier.issn0022-3751en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132540-
dc.description.abstractModulation of cytoplasmic free Ca2+ concentration ([Ca2+]i) by receptor-mediated generation of inositol 1,4,5-trisphosphate (InsP3) and activation of its receptor (InsP3R), a Ca2+-release channel in the endoplasmic reticulum, is a ubiquitous signalling mechanism. A fundamental aspect of InsP3-mediated signalling is the graded release of Ca2+ in response to incremental levels of stimuli. Ca2+ release has a transient fast phase, whose rate is proportional to [InsP3], followed by a much slower one even in constant [InsP3]. Many schemes have been proposed to account for quantal Ca2+ release, including the presence of heterogeneous channels and Ca2+ stores with various mechanisms of release termination. Here, we demonstrate that mechanisms intrinsic to the single InsP3R channel can account for quantal Ca2+ release. Patch-clamp electrophysiology of isolated insect Sf9 cell nuclei revealed a consistent and high probability of detecting functional endogenous InsP3R channels, enabling InsP3-induced channel inactivation to be identified as an inevitable consequence of activation, and allowing the average number of activated channels in the membrane patch (NA) to be accurately quantified. InsP3-activated channels invariably inactivated, with average duration of channel activity reduced by high [Ca2+]i and suboptimal [InsP3]. Unexpectedly, NA was found to be a graded function of both [Ca2+]i and [InsP3]. A qualitative model involving Ca2+-induced InsP3R sequestration and inactivation can account for these observations. These results suggest that apparent heterogeneous ligand sensitivity can be generated in a homogeneous population of InsP3R channels, providing a mechanism for graded Ca2+ release that is intrinsic to the InsP3R Ca2+ release channel itself. © 2006 The Authors. Journal compilation © 2006 The Physiological Society.en_HK
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0022-3751en_HK
dc.relation.ispartofJournal of Physiologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleGraded recruitment and inactivation of single InsP3 receptor Ca2+-release channels: Implications for quartal Ca2+releaseen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, KH: kingho.cheung@hku.hken_HK
dc.identifier.authorityCheung, KH=rp01463en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1113/jphysiol.2006.109504en_HK
dc.identifier.pmid16644799-
dc.identifier.pmcidPMC1779751-
dc.identifier.scopuseid_2-s2.0-33744905361en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33744905361&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume573en_HK
dc.identifier.issue3en_HK
dc.identifier.spage645en_HK
dc.identifier.epage662en_HK
dc.identifier.eissn1469-7793-
dc.identifier.isiWOS:000239154200005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridIonescu, L=36658318500en_HK
dc.identifier.scopusauthoridCheung, KH=14007487800en_HK
dc.identifier.scopusauthoridVais, H=6602154738en_HK
dc.identifier.scopusauthoridMak, DOD=35587181700en_HK
dc.identifier.scopusauthoridWhite, C=7404153650en_HK
dc.identifier.scopusauthoridFoskett, JK=7005723620en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats