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 microns ) 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 Ca(2+)-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.
Cheng
H
H
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, USA.
Lederer
M R
MR
Xiao
R P
RP
Gómez
A M
AM
Zhou
Y Y
YY
Ziman
B
B
Spurgeon
H
H
Lakatta
E G
EG
Lederer
W J
WJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D005071:Evoked Potentials; D006321:Heart / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D009200:Myocardial Contraction; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D013050:Spectrometry, Fluorescence
D002118:Calcium