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


METHODS
Isolated guinea pig ventricular myocytes were studied at room temperature and at 37 degrees 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 degrees 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 degrees C, insulin increased the extent of myocyte contraction despite producing a significant decrease in I(Ca,L) amplitude.


CONCLUSIONS
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).
Pabbathi
V K
VK
Bristol Heart Institute, University of Bristol, Bristol, UK.
Suleiman
M S
MS
Hancox
J C
JC
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques
D020746:Calcium Channels, L-Type; D007004:Hypoglycemic Agents; D007328:Insulin