Cytosolic Ca2+ concentration decreases in diabetic rat myocytes

Time for primary review 24 days. Diabetes mellitus has been shown to be associated with heart failure of unknown origin, which is termed ‘diabetic cardiomyopathy’ 1. Regan et al. 2have shown that the small vessel lesions in diabetes mellitus have little or no relation to diabetic cardiomyopathy, suggesting that the contractile function of the diabetic cardiomyopathy was primarily defective. Although many studies have been performed to reveal cellular and subcellular derangement in diabetic cardiomyopathy 3–6, the precise mechanism is still unknown. It has been reported that Ca2+ metabolism in diabetic myocardium has several abnormalities, including a decreased activity of Ca2+-ATPase in sarcoplasmic reticulum (SR) 7, 8and sarcolemma 9, 10. It has also been reported that the activity of Na+/Ca2+ exchange is lower in diabetic myocardium 10. These reports have suggested that Ca2+ overload may be involved in the pathogenesis of diabetic cardiomyopathy 3. Although it has been shown that certain mechanical and electrophysiological features in diabetic rats correlate well with conditions of intracellular Ca2+ overload 11, 12, direct measurement of the cytosolic Ca2+ concentration (Ca2+i) has not been made previously. The most popular method for measuring Ca2+i uses fluorescent probes such as fura-2 and indo-1 13. We have reported that Ca2+i of unstimulated rat myocytes isolated from insulin-dependent diabetes mellitus (IDDM) was lower than that of normal myocytes using fura-2 (53±3 nM in diabetic myocytes and 75±5 nM in normal myocytes, mean±s.e.; P <0.01) 14. Recently, Lagadic-Gossmann et al. 15also reported that basal Ca2+i level was lower in diabetic myocytes using indo-1. Horackova and Murphy 16have reported that the Ca2+ content is decreased in diabetic rat … * Corresponding author. Tel. +81 53 435-2391; Fax +81 53 435-2394.