Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition

• Published in: Circulation research Vol. 88; no. 2; pp. 181 - 187
• Main Authors: Overend, C L, Eisner, D A, O’Neill, S C
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 02.02.2001; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Aniline Compounds; Animals; Biological and medical sciences; Cadmium - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - metabolism; Calcium Signaling - physiology; Calcium-Transporting ATPases - antagonists & inhibitors; Calcium-Transporting ATPases - metabolism; Cardiology. Vascular system; Cells, Cultured; Coronary heart disease; Cyanides - pharmacology; Deoxyglucose - pharmacology; Fluorescent Dyes; Heart; Heart Ventricles - cytology; Heart Ventricles - metabolism; Intracellular Fluid - metabolism; Medical sciences; Microscopy, Confocal; Myocardium - cytology; Myocardium - metabolism; Patch-Clamp Techniques; Rats; Ryanodine Receptor Calcium Release Channel - metabolism; Sarcoplasmic Reticulum - metabolism; Xanthenes; Heart; Animal model; Rat; Rodentia; Electrophysiology; Cardiovascular disease; Smooth muscle; Heart ventricle; Ionic current; Metabolism; Coronary heart disease; Myocardial disease; Vascular disease; Vertebrata; Mammalia; Calcium ion; Ischemia; Sarcoplasmic reticulum; Animal; Myocardium; Circulatory system; Inhibition; Intracellular; Release
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.88.2.181

ABSTRACT —Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca and the perforated patch-clamp technique to measure SR Ca content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca (sparks and waves of Ca-induced Ca release), increased SR Ca content (79.4±5.7 to 115.2±6.6 μmol/L cell volume [mean±SEM;P <0.001]), and, after a wave of Ca release, slower reuptake of Ca into the SR (rate constant of fall of Ca reduced from 8.5±1.1 s in control to 5.2±0.4 s in metabolic inhibition [P <0.01]). Inhibition of L-type Ca channels with Cd (100 μmol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca sparks. These results are evidence of inhibition of both Ca release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca content at the time of reduced frequency of spontaneous release of Ca shows that the dominant effect of metabolic inhibition is to inhibit release of Ca from the SR, allowing the accumulation of greater than normal amounts of Ca. In the context of ischemia, this extra accumulation of Ca would present a risk of potentially arrhythmogenic, spontaneous release of Ca on reperfusion of the tissue.