Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca2+ Transient in Rat Ventricular Myocytes

• Published in: Circulation research 2002-10, Vol.91 (7), p.585-593
• Main Authors: Díaz, M E, Eisner, D A, O’Neill, S C
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium Signaling - drug effects; Cardiac dysrhythmias; Cardiology. Vascular system; Cells, Cultured; Heart; Heart Ventricles - cytology; Heart Ventricles - metabolism; Hydrogen-Ion Concentration; Kinetics; Medical sciences; Microscopy, Confocal; Myocardial Contraction; Patch-Clamp Techniques; Rats; Rats, Wistar; Ryanodine Receptor Calcium Release Channel - metabolism; Sarcoplasmic Reticulum - metabolism; Systole; Tetracaine - pharmacology; Ventricular Function
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.0000035527.53514.c2

ABSTRACT—Sarcoplasmic reticulum (SR) Ca release, through the ryanodine receptor (RyR), is essential for the systolic Ca transient and thus the cardiac contractile function. The aim of this study was to examine the effects on the spatial organization of the systolic Ca transient of depressing RyR open probability (Po) with tetracaine or intracellular acidification. Voltage-clamped, fluo-3–loaded myocytes were studied using confocal microscopy. Depressing RyR Po increased the variability of the Ca transient amplitude between different regions of the cell. This variability often produced alternans with a region producing large and small transients alternately. In addition, the raising phase of the Ca transient became biphasic. The initial phase was constant but the second was variable and propagated as a wave through part of the cell. That both phases involved SR Ca release was shown by their reduction by caffeine. Regional [Ca]i alternans was accompanied by a much smaller degree of alternans at the whole cell level. We suggest that, in tetracaine or acidosis, the initial phase of the Ca transient results from Ca release via RyRs directly activated by adjacent L-type Ca channels. At some sites, this will activate neighboring RyRs and a Ca wave will propagate via activation of other RyRs. This work is the first demonstration that decreased RyR Po alone can produce disarray of the Ca release process and initiate alternans.