Insulin and the resting potential of hypoxic substrate-deprived myocardium.
Insulin stimulates ionic transport by the sodium pump and induces hyperpolarization in skeletal and cardiac muscle among other cells. The insulin-induced hyperpolarization in most cases can be inhibited by exposure to cardiac glycosides or metabolic inhibition. However, extracellular accumulation of K ions leaking from hypoxic cells in superfused preparations may distort the effects of insulin on the resting potential. We used standard microelectrode techniques and perfused rabbit hearts submitted to hypoxia and substrate deprivation to reinvestigate the effects of insulin (6.4 nM) on the membrane potential. The membrane depolarized by about 6 mV and the action potential was reduced to a sharp spike without overshoot. Insulin restored the resting potential to control values but did not change the action potential configuration substantially. The insulin-induced repolarization was not due to reuptake of potassium as revealed by spectrophotometric determinations of myocardial K content. In addition, the diffusion component of the resting potential measured after inhibition of the sodium pump with 10(-4) M ouabain was not modified by insulin. Our results suggest that an increase in the contribution of electrogenic Na extrusion to the resting potential underlies the repolarizing effect of insulin of hypoxic substrate-deprived myocardium.
Ruiz-Ceretti
E
E
Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Qué., Canada.
DeLorenzi
F
F
Lafond
J S
JS
Chartier
D
D
D000818:Animals; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits
D007328:Insulin; D011188:Potassium; D010100:Oxygen