LOCALIZED INTRACELLULAR CALCIUM SIGNALING IN MUSCLE: Calcium Sparks and Calcium Quarks

Subcellularly localized Ca²⁺ signals in cardiac and skeletal muscle have recently been identified as elementary Ca²⁺ signaling events. The signals, termed Ca²⁺ sparks and Ca²⁺ quarks, represent openings of Ca²⁺ release channels located in the membrane of the sarcoplasmic reticulum (SR). In cardiac muscle, the revolutionary discovery of Ca²⁺ sparks has allowed the development of a fundamentally different concept for the amplification of Ca²⁺ signals by Ca²⁺-induced Ca²⁺ release. In such a system, a graded amplification of the triggering Ca²⁺ signal entering the myocyte via L-type Ca²⁺ channels is accomplished by a recruitment process whereby individual SR Ca²⁺ release units are locally controlled by L-type Ca²⁺ channels. In skeletal muscle, the initial SR Ca²⁺ release is governed by voltage-sensors but subsequently activates additional Ca²⁺ sparks by Ca²⁺-induced Ca²⁺ release from the SR. Results from studies on elementary Ca²⁺ release events will improve our knowledge of muscle Ca²⁺ signaling at all levels of complexity, from the molecule to normal cellular function, and from the regulation of cardiac and skeletal muscle force to the pathophysiology of excitation-contraction coupling.