Luminal Ca(2+) content regulates intracellular Ca(2+) release in subepicardial myocytes of intact beating mouse hearts: effect of exogenous buffers.
Ca(+)-induced Ca(2+) release tightly controls the function of ventricular cardiac myocytes under normal and pathological conditions. Two major factors contributing to the regulation of Ca(2+) release are the cytosolic free Ca(2+) concentration and sarcoplasmic reticulum (SR) Ca(2+) content. We hypothesized that the amount of Ca(2+) released from the SR during each heart beat strongly defines the refractoriness of Ca(2+) release. To test this hypothesis, EGTA AM, a high-affinity, slow-association rate Ca(2+) chelator, was used as a tool to modify luminal SR Ca(2+) content. An analysis of the cytosolic and luminal SR Ca(2+) dynamics recorded from the epicardial layer of intact mouse hearts indicated that the presence of EGTA reduced the diastolic SR free Ca(2+) concentration and fraction of SR Ca(2+) depletion during each beat. In addition, this maneuver shortened the refractory period and accelerated the restitution of Ca(2+) release. As a consequence of the accelerated restitution, the frequency dependence of Ca(2+) alternans was significantly shifted toward higher heart rates, suggesting a role of luminal SR Ca(2+) in the genesis of this highly arrhythmogenic phenomenon. Thus, intra-SR Ca(2+) dynamics set the refractoriness and frequency dependence of Ca(2+) transients in subepicardial ventricular myocytes.
Kornyeyev
Dmytro
D
School of Engineering, Univ. of California-Merced, 5200 N. Lake Rd., Merced, CA 95343, USA.
Reyes
Mariano
M
Escobar
Ariel L
AL
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D008962:Models, Theoretical; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010496:Pericardium / Q000166:cytology / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D002021:Buffers; D004533:Egtazic Acid; C046770:EGTA acetoxymethyl ester; D002118:Calcium
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