title: Conformational activation of Ca2+ entry by depolarization of skeletal myotubes.
abstract: Store-operated Ca(2+) entry (SOCE) occurs in diverse cell types in response to depletion of Ca(2+) within the endoplasmic/sarcoplasmic reticulum and functions both to refill these stores and to shape cytoplasmic Ca(2+) transients. Here we report that in addition to conventional SOCE, skeletal myotubes display a physiological mechanism that we term excitation-coupled Ca(2+) entry (ECCE). ECCE is rapidly initiated by membrane depolarization. Like excitation-contraction coupling, ECCE is absent in both dyspedic myotubes that lack the skeletal muscle-type ryanodine receptor 1 and dysgenic myotubes that lack the dihydropyridine receptor (DHPR), and is independent of the DHPR l-type Ca(2+) current. Unlike classic SOCE, ECCE does not depend on sarcoplasmic reticulum Ca(2+) release. Indeed, ECCE produces a large Ca(2+) entry in response to physiological stimuli that do not produce substantial store depletion and depends on interactions among three different Ca(2+) channels: the DHPR, ryanodine receptor 1, and a Ca(2+) entry channel with properties corresponding to those of store-operated Ca(2+) channels. ECCE may provide a fundamental means to rapidly maintain Ca(2+) stores and control important aspects of Ca(2+) signaling in both muscle and nonmuscle cells.
authors.affiliation: Department of Molecular Biosciences and Center for Children's Environmental Health and Disease Prevention, University of California, Davis, CA 95616, USA.
authors.forename: Gennady
authors.initials: G
authors.lastname: Cherednichenko
authors.forename: Alanna M
authors.initials: AM
authors.lastname: Hurne
authors.forename: James D
authors.initials: JD
authors.lastname: Fessenden
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
authors.forename: Paul D
authors.initials: PD
authors.lastname: Allen
authors.forename: Kurt G
authors.initials: KG
authors.lastname: Beam
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D004558:Electric Stimulation; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium