Cytosolic Ca2+ concentration decreases in diabetic rat myocytes.

Diabetes mellitus has been shown to be associated with heart failure of unknown origin, which is termed ‘diabetic w x w x cardiomyopathy’ 1 . Regan et al. 2 have 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 w x in diabetic cardiomyopathy 3–6 , the precise mechanism is still unknown. It has been reported that Ca metabolism in diabetic myocardium has several abnormalities, including a decreased activity of Ca-ATPase in sarcoplasmic reticulum Ž . w x w x SR 7,8 and sarcolemma 9,10 . It has also been reported that the activity of NarCa exchange is lower in diaw x betic myocardium 10 . These reports have suggested that Ca overload may be involved in the pathogenesis of w x diabetic cardiomyopathy 3 . Although it has been shown that certain mechanical and electrophysiological features in diabetic rats correlate well with conditions of intracellular 2q w x Ca overload 11,12 , direct measurement of the cytosolic 2q Žw 2qx . Ca concentration Ca has not been made previi w 2qx ously. The most popular method for measuring Ca i w x uses fluorescent probes such as fura-2 and indo-1 13 . We w 2qx have reported that Ca of unstimulated rat myocytes i Ž . isolated from insulin-dependent diabetes mellitus IDDM was lower than that of normal myocytes using fura-2 Ž53"3 nM in diabetic myocytes and 75"5 nM in normal . w x myocytes, mean " s.e.; P 0.01 14 . Recently, w x Lagadic-Gossmann et al. 15 also reported that basal w 2qx Ca level was lower in diabetic myocytes using indo-1. i w x 2q Horackova and Murphy 16 have reported that the Ca content is decreased in diabetic rat myocytes using the