Excitation contraction coupling in heart: New insights from Ca²⁺ sparks

Ca²⁺ sparks, the elementary units of sarcoplasmic reticulum (SR) Ca²⁺ release in cardiac, smooth and skeletal muscle are localized (2-4 μm) increases in intracellular Ca²⁺ concentration, [Ca²⁺](i), that last briefly (30-100 ms). These Ca²⁺ sparks arise from the openings of a single SR Ca²⁺ release channel (ryanodine receptor, RyR) or a few RyRs acting in concert. In heart muscle, Ca²⁺ sparks can occur spontaneously in quiescent cells at a low rate (100 s^-1 per cell). Identical Ca²⁺ sparks are also triggered by depolarization because the voltage-gated sarcolemmal L-type Ca²⁺ channels (dihydropyridine receptors, DHPRs) locally increase [Ca²⁺](i) and thereby activate the RyRs by Ca²⁺-induced Ca²⁺ release (CICR). The exquisite responsiveness of this process, reflected by the ability of even a single DHPR to activate a Ca²⁺ spark, is perhaps due to the large local increase in [Ca²⁺](i) in the vicinity of the RyR that is a consequence of the close apposition of the DHPRs and the RyRs. In this review we examine our current understanding of cardiac excitation-contraction (EC) coupling in light of recent studies on the elementary Ca²⁺ release events or Ca²⁺ sparks. In addition, we further characterized Ca²⁺ spark properties in rat and mouse heart cells. Specifically we have determined that: (i) Ca²⁺ sparks occur at the junctions between the transverse-tubules and the SR in both species; (ii) Ca²⁺ sparks are asymmetric, being 18% longer in the longitudinal direction than in the transverse direction; and (iii) Ca²⁺ sparks individually do not produce measurable sarcomere shortening (< 1%). These results are discussed with respect to local activation of the RyRs, the stability of CICR, Ca²⁺ diffusion, and the theory of EC coupling.