title: Involvement of multiple intracellular release channels in calcium sparks of skeletal muscle.
abstract: In many types of muscle, intracellular Ca(2+) release for contraction consists of brief Ca(2+) sparks. Whether these result from the opening of one or many channels in the sarcoplasmic reticulum is not known. Examining massive numbers of sparks from frog skeletal muscle and evaluating their Ca(2+) release current, we provide evidence that they are generated by multiple channels. A mode is demonstrated in the distribution of spark rise times in the presence of the channel activator caffeine. This finding contradicts expectations for single channels evolving reversibly, but not for channels in a group, which collectively could give rise to a stereotyped spark. The release channel agonists imperatoxin A, ryanodine, and bastadin 10 elicit fluorescence events that start with a spark, then decay to steady levels roughly proportional to the unitary conductances of 35%, 50%, and 100% that the agonists, respectively, promote in bilayer experiments. This correspondence indicates that the steady phase is produced by one open channel. Calculated Ca(2+) release current decays 10- to 20-fold from spark to steady phase, which requires that six or more channels be open during the spark.
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush University, 1750 West Harrison Street, Chicago, IL 60612, USA.
authors.forename: A
authors.initials: A
authors.lastname: González
authors.forename: W G
authors.initials: WG
authors.lastname: Kirsch
authors.forename: N
authors.initials: N
authors.lastname: Shirokova
authors.forename: G
authors.initials: G
authors.lastname: Pizarro
authors.forename: G
authors.initials: G
authors.lastname: Brum
authors.forename: I N
authors.initials: IN
authors.lastname: Pessah
authors.forename: M D
authors.initials: MD
authors.lastname: Stern
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: E
authors.initials: E
authors.lastname: Ríos
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000502:physiology*; D011894:Rana pipiens
chemical_list: D015220:Calcium Channels; D002118:Calcium