Initiation and termination of calcium sparks in skeletal muscle.

Abstract

Depolarization of the transverse tubules of a skeletal muscle fiber initiates release of Ca2+ ions via ryanodine receptor (RyR) Ca2+ release channels in the adjacent junctional sarcoplasmic reticulum (SR) membrane at triad junctions. Discrete localized Ca2+ release events (Ca2+ "sparks") detected by confocal imaging of Ca2+ indicator-containing muscle fibers may arise from the coordinated opening of a small group of RyR Ca2+ release channels, or possibly even from the opening of a single channel. These discrete Ca2+ release events originate at triad junctions and can be gated by fiber depolarization or by physiological cytosolic ligands (e.g., Ca2+ and Mg2+) in functioning muscle fibers. The global increase in myoplasmic Ca2+ during fiber depolarization appears to consist of the summation of huge numbers of Ca2+ sparks initiated during a brief time interval. Study of Ca2+ sparks thus offers a unique window into the operation of groups of SR Ca2+ release channels or individual channels within the normal structural and molecular environment of a functioning fiber. The Ca2+ release underlying a spark appears to turn on and off abruptly respectively at the start and at the peak of a spark. Under many stimuli, the frequency and/or pattern of occurrence of the Ca2+ sparks is altered, indicating changes in the closed time (or opening rate) of the channels that initiate the sparks. In contrast, the average values of the spatio-temporal properties of the individual events generally remain unchanged, indicating constancy of channel open time and constancy of total Ca2+ efflux via the channels generating a spark. A few conditions that alter the average properties of Ca2+ sparks provide rare insights regarding the open-time of the Ca2+ channels generating the Ca2+ spark.