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

H. Cheng, M. R. Lederer, R. P. Xiao, A. M. Gómez, Y. Y. Zhou, B. Ziman, H. Spurgeon, E. G. Lakatta, W. J. Lederer

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)129-140
Number of pages12
JournalCell Calcium
Volume20
Issue number2
DOIs
StatePublished - Aug 1996
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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