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Article: Mode switching is the major mechanism of ligand regulation of InsP 3 receptor calcium release channels

TitleMode switching is the major mechanism of ligand regulation of InsP 3 receptor calcium release channels
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2007
PublisherRockefeller University Press. The Journal's web site is located at www.jgp.org/
Citation
Journal Of General Physiology, 2007, v. 130 n. 6, p. 631-645 How to Cite?
AbstractThe inositol 1,4,5-trisphosphate (InsP 3) receptor (InsP 3R) plays a critical role in generation of complex Ca 2+ signals in many cell types. In patch clamp recordings of isolated nuclei from insect Sf9 cells, InsP 3R channels were consistently detected with regulation by cytoplasmic InsP 3 and free Ca 2+ concentrations ([Ca 2+] i) very similar to that observed for vertebrate InsP 3R. Long channel activity durations of the Sf9-InsP 3R have now enabled identification of a novel aspect of InsP 3R gating: modal gating. Using a novel algorithm to analyze channel modal gating kinetics, InsP 3R gating can be separated into three distinct modes: a low activity mode, a fast kinetic mode, and a burst mode with channel open probability (P o) within each mode of 0.007 ± 0.002, 0.24 ± 0.03, and 0.85 ± 0.02, respectively. Channels reside in each mode for long periods (tens of opening and closing events), and transitions between modes can be discerned with high resolution (within two channel opening and closing events). Remarkably, regulation of channel gating by [Ca 2+] i and [InsP 3] does not substantially alter channel P o within a mode. Instead, [Ca 2+] i and [InsP 3] affect overall channel P o primarily by changing the relative probability of the channel being in each mode, especially the high and low P o modes. This novel observation therefore reveals modal switching as the major mechanism of physiological regulation of InsP 3R channel activity, with implications for the kinetics of Ca 2+ release events in cells. © The Rockefeller University Press.
Persistent Identifierhttp://hdl.handle.net/10722/132535
ISSN
2015 Impact Factor: 4.511
2015 SCImago Journal Rankings: 3.061
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorIonescu, Len_HK
dc.contributor.authorWhite, Cen_HK
dc.contributor.authorCheung, KHen_HK
dc.contributor.authorShuai, Jen_HK
dc.contributor.authorParker, Ien_HK
dc.contributor.authorPearson, JEen_HK
dc.contributor.authorFoskett, JKen_HK
dc.contributor.authorMak, DODen_HK
dc.date.accessioned2011-03-28T09:26:03Z-
dc.date.available2011-03-28T09:26:03Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of General Physiology, 2007, v. 130 n. 6, p. 631-645en_HK
dc.identifier.issn0022-1295en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132535-
dc.description.abstractThe inositol 1,4,5-trisphosphate (InsP 3) receptor (InsP 3R) plays a critical role in generation of complex Ca 2+ signals in many cell types. In patch clamp recordings of isolated nuclei from insect Sf9 cells, InsP 3R channels were consistently detected with regulation by cytoplasmic InsP 3 and free Ca 2+ concentrations ([Ca 2+] i) very similar to that observed for vertebrate InsP 3R. Long channel activity durations of the Sf9-InsP 3R have now enabled identification of a novel aspect of InsP 3R gating: modal gating. Using a novel algorithm to analyze channel modal gating kinetics, InsP 3R gating can be separated into three distinct modes: a low activity mode, a fast kinetic mode, and a burst mode with channel open probability (P o) within each mode of 0.007 ± 0.002, 0.24 ± 0.03, and 0.85 ± 0.02, respectively. Channels reside in each mode for long periods (tens of opening and closing events), and transitions between modes can be discerned with high resolution (within two channel opening and closing events). Remarkably, regulation of channel gating by [Ca 2+] i and [InsP 3] does not substantially alter channel P o within a mode. Instead, [Ca 2+] i and [InsP 3] affect overall channel P o primarily by changing the relative probability of the channel being in each mode, especially the high and low P o modes. This novel observation therefore reveals modal switching as the major mechanism of physiological regulation of InsP 3R channel activity, with implications for the kinetics of Ca 2+ release events in cells. © The Rockefeller University Press.en_HK
dc.languageengen_US
dc.publisherRockefeller University Press. The Journal's web site is located at www.jgp.org/en_HK
dc.relation.ispartofJournal of General Physiologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleMode switching is the major mechanism of ligand regulation of InsP 3 receptor calcium release channelsen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, KH: kingho.cheung@hku.hken_HK
dc.identifier.authorityCheung, KH=rp01463en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1085/jgp.200709859en_HK
dc.identifier.pmid17998395-
dc.identifier.pmcidPMC2151663-
dc.identifier.scopuseid_2-s2.0-36549079005en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36549079005&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume130en_HK
dc.identifier.issue6en_HK
dc.identifier.spage631en_HK
dc.identifier.epage645en_HK
dc.identifier.isiWOS:000251512000009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridIonescu, L=36658318500en_HK
dc.identifier.scopusauthoridWhite, C=7404153650en_HK
dc.identifier.scopusauthoridCheung, KH=14007487800en_HK
dc.identifier.scopusauthoridShuai, J=7005124608en_HK
dc.identifier.scopusauthoridParker, I=35550719600en_HK
dc.identifier.scopusauthoridPearson, JE=7401927753en_HK
dc.identifier.scopusauthoridFoskett, JK=7005723620en_HK
dc.identifier.scopusauthoridMak, DOD=35587181700en_HK

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