| Summary: | 博士 === 國防醫學院 === 醫學科學研究所 === 95 === Background: An increase in intracellular calcium transients is responsible for the positive inotropic effect of insulin on human myocardium, but the mechanisms involved in this increase in [Ca2+]i remain unclear.
Materials and Methods: We studied isolated trabeculae or cardiomyocytes from end-stage failing hearts of 38 patients undergoing heart transplantation. The effect of insulin on isometric twitch force (37°C, 0.5 Hz) and L-type Ca2+ current (whole-cell voltage clamp) was assessed.
Results: Crystalline insulin increased the contractile force in a dose-dependent manner (0.01 to 10 µM), with a maximum increase of 458% (p<0.05) at 1 mol/liter. It also increased L-type Ca2+ peak current density by 26 6% (p < 0.05). This insulin-mediated positive inotropic effect was unchanged in the presence of propranolol (1 µM). Positive inotropy was partially independent of glucose. L-type Ca2+ channel blockade (diltiazem, 5 µM), and sarcoplasmic reticulum (SR) Ca2+-release channel blockade (ryanodine, 0.1 µM) did not affect the inotropic response to insulin. However, blockade of SR Ca2+-ATPase (cyclopiazonic acid, 10 µM), inhibition of Na+-H+ exchange (HOE642, 10 µM), and inhibition of Na+-Ca2+ exchange (SEA0400, 1 µM) partially prevented the inotropic response to insulin.
Conclusions: Positive inotropy of insulin was not related to catecholamine release and subsequent stimulation of β-adrenergic receptor, but it may enhance the activity of SR Ca2+-ATPase and trans-sarcolemmal Ca2+ entry, mainly via reverse-mode Na+-Ca2+ exchange and insulin-mediated activation of Na+-H+ exchange. We hypothesize that these changes in [Ca2+]i might be secondary to the activation of reverse-mode Na+-Ca2+ exchange, presumably via elevated intracellular Na+ concentration.
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