Paradoxical effects of insulin on cardiac L-type calcium current and on contraction at physiological temperature

Abstract

Aims/hypothesis. L-type calcium current (I Ca,L ) is a major determinant of mammalian cardiac contraction, and data from studies performed at room temperature suggest that this current is stimulated by insulin. This investigation aimed to determine whether or not insulin stimulates cardiac I Ca,L at 37°C. Methods. Isolated guinea pig ventricular myocytes were studied at room temperature and at 37°C. Myocytes were either field stimulated or whole-cell voltage clamped, and cell shortening was measured using video edge detection. Results. Insulin stimulated I Ca,L at ambient temperature. However, at 37°C the effect of insulin was to decrease rather than to increase I Ca,L . This action was concentration dependent and was not associated with voltage shifts in steady-state activation or inactivation properties of I Ca,L . At 37°C, insulin increased the extent of myocyte contraction despite producing a significant decrease in I Ca,L amplitude. Conclusions/interpretation. The findings of this study indicate that temperature is a key experimental variable in the study of the physiological actions of insulin. Furthermore, the increase in cardiac cell contraction by insulin at physiological temperature is not due to an increase in I Ca,L , but is probably due to stimulation of excitation-contraction coupling downstream of I Ca,L .

Cholesterol Depletion Alters Cardiomyocyte Subcellular Signaling and Increases Contractility

“…Although this difference may seem trivial, there are multiple reports of the temperature dependence of cardiomyocyte contractility and calcium handling, and in some cases opposite effects are seen at room temperature vs. 37°C. [ 36 ],[ 37 ],[ 38 ],[ 39 ]…”