title: Ultra-rapid activation and deactivation of store-operated Ca(2+) entry in skeletal muscle.
abstract: Skeletal muscle is highly specialized for the rapid delivery of Ca(2+) to the contractile apparatus during excitation-contraction coupling (EC coupling). Previous studies have shown the presence of a relatively fast-activated store-operated Ca(2+) entry (SOCE) mechanism (<1s) to be present in skeletal muscle, unlike the situation occurring in non-excitable cells. We simultaneously imaged [Ca(2+)] in the t-system and cytoplasm in mechanically skinned fibers during SR Ca(2+) release and observed both cell-wide Ca(2+) release and Ca(2+) waves. SOCE activation followed cell-wide Ca(2+) release from high sarcoplasmic reticulum (SR) [Ca(2+)] ([Ca(2+)](SR)) by seconds, consistent with depletion of [Ca(2+)](SR) to an absolute threshold for SOCE and an unformed SOCE complex at high [Ca(2+)](SR). Ca(2+) waves occurred at low [Ca(2+)](SR), close to the threshold for SOCE, minimizing the time between Ca(2+) release and Ca(2+) influx. Local activation of SOCE during Ca(2+) waves occurred in approximately 27ms following local initiation of SR depletion indicating a steep relationship between [Ca(2+)](SR) and SOCE activation. Most of this delay was due to slow release of Ca(2+) from SR, leaving only milliseconds at most for the activation of Ca(2+) entry following store depletion. SOCE was also observed to deactivate effectively instantly during store refilling at low [Ca(2+)](SR). These rapid kinetics of SOCE persisted as subsequent Ca(2+) waves propagated along the fiber. Thus we show for the first time millisecond activation and deactivation of SOCE during low amplitude [Ca(2+)](SR) oscillations at low [Ca(2+)](SR). To account for the observed Ca(2+) movements we propose the SOCE complex forms during the progressive depletion of [Ca(2+)](SR) prior to reaching the activation threshold of SOCE and this complex remains stable at low [Ca(2+)](SR).
authors.affiliation: The University of Queensland, Brisbane, Australia.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Edwards
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Murphy
authors.forename: Tanya R
authors.initials: TR
authors.lastname: Cully
authors.forename: Frederic
authors.initials: F
authors.lastname: von Wegner
authors.forename: Oliver
authors.initials: O
authors.lastname: Friedrich
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Launikonis
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000032:analysis; D002478:Cells, Cultured; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071740:ORAI1 Protein; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; D002118:Calcium