Alterations of membrane potential and Ca2+ flux of sarcoplasmic reticulum vesicles in ischemic myocardium

The sequence of contraction-relaxation for myocardial cells is believed to be linked to Ca2+ flux across the sarcoplasmic reticulum. Alterations of sarcoplasmic reticulum function during ischemia may result in depressing the myocardial contraction-relaxation sequence. This study examines the relationship between the membrane potential and Ca2+ flux across sarcoplasmic reticulum vesicles isolated from non-ischemic and ischemic myocardium. Ischemic myocardium was produced by ligating the coronary artery of swine hearts for 15 and 30 minutes. Membrane potential was determined by use of the fluorescence-sensitive dye, 3,3'-diethylthiadicarbocyanine, and Ca2+ uptake was studied spectrophotometrically with the use of murexide. Results are as follows: (1) membrane potential and Ca2+ uptake by sarcoplasmic reticulum from ischemic myocardium progressively decreased with the length of ischemia; and (2) preincubation of sarcoplasmic reticulum from non-ischemic myocardium with deoxycholate (0.01 approximately 0.09 percent) resulted in progressively decreasing membrane potential and Ca2+ uptake. Apparently a correlation exists between membrane potential and the rate of Ca2+ uptake. These results suggest that membrane characteristics of sarcoplasmic reticulum are altered within as early as 15 minutes of the onset of ischemia. Alteration of membrane permeability in sarcoplasmic reticulum from ischemic myocardium may be responsible for the observed decrease in membrane potential and Ca2+ uptake.