RATIONALE In cardiac muscle, Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) is mediated by ryanodine receptor (RyR) Ca(2+) release channels. The inherent positive feedback of CICR is normally well-controlled. Understanding this control mechanism is a priority because its malfunction has life-threatening consequences. OBJECTIVE We show that CICR local control is gove...

The release mechanism regulating SR Ca2+ homeostasis is significantly more sensitive than the uptake mechanisms. The exquisite sensitivity exhibited by ryanodine-sensitive Ca2+ channel complexes (i.e., ryanodine receptors, RyRs) to functional perturbation by chemically diverse sulfhydryl-modifying compounds can include phases of activation and inhibition that are dependent on the concentration ...

Calmodulin is a ubiquitous Ca2+ binding protein that binds to ryanodine rectors (RyR) and is thought to modulate its activity. Here we evaluated the effects of recombinant calmodulin on the rate of occurrence and spatial properties of Ca2+ sparks as an assay of activation in saponin-permeabilized mouse myofibers. Control myofibers exhibited a time-dependent increase and subsequent decrease in s...