Insulin and the resting potential of hypoxic substrate-deprived myocardium

Abstract

the resting potential of hypoxic substrate-deprived myocardium. Can. I. Physiol. Pharmacol. 66: 202-206. 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 cats 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 p d u s e d rabbit hearts submitted to hypxia and substrate deprivation $0 reinvestigate the effects of insulin (6.4 nM) on the membrane potential. The membrane deplaized 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-% ouabain was not modified by insulin. Our results suggest that an increase in the contribution of electrogenic Na extmslon to the resting potential underlies the repolarizing effect (BE insulin of hypoxic substrate-deprived myocardium.RUIZ-CERETTI, E., DELORENZI, F., LAFOND, J. S., et CHARTIER, D. 1988. Insulin and the resting potential sf hypxic substrate-deprived myocardium. Can. I . Physiol . Phxmacol. 66 : 202-206. L9insuline stimule la p o m p Na-K et hyperpolarise la membrane de plusieurs types de cellules dont les muscles squelettique et cardiaque. Dans la plupart des cas, cette hyperpolarisation peut-&re inhibde par une exposition prialable B I'ouabaine ou par inhibition mitabolique. Cependant, I'accumulation extracellulaire d'ions K chez des priparations supedusies peut masquer les effets de l'insuline sur le potentiel de repos. Nsus avons appliquk Ea technique de rnicroilectrodes h des coeurs de lapin pPfusCs, soumis 2 I'hypoxie et au manque de substrat, afin de reinvestiguer les effets de E'insuline (6,4 nM). L'inhibition mttabslique prduisait une dCpolaisation membranaire d'environ 6 mV et rkduisait le potentiel d'action B un court pic sans << overshoot a. L'insuline rttablissait B e potentiel de repos & des valeurs contr6Bes mais ne modifiait pas significativernent B a morphologie du potentiel d9action. La repolarisation n'Ctait pas due B une captation accrue du potassium tel que montrd par la ddtermination spectrophotom6trique du contenu potassique du myocarde. De plus, la composante diffusionnelle du potentiel de repos mesbarke aprks I'application Be l'ouabaine B lo-%, n'itait pas modifide p a lqI'insuline. Nos rksultats suggkreent qu'une augmentation de la contribution de la p m p e Na-K rau potentiel de repos est sous-jacente B l'effet repolarisant de I'insuline chez le myscade hypoxique en absence...

Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels

“…Acute stimulation of the Na + –K + ‐ATPase by insulin increases the intracellular uptake of K + and produce hypokalaemia. Insulin has been reported to stimulate ionic transport by the sodium pump and induce hyperpolarization in skeletal and cardiac muscle among other cells (Ruiz‐Ceretti, DeLorenzi, Lafond & Chartier, 1988). Insulin, at low doses, can be an effective antiarrhythmic agent against ouabain‐induced arrhythmias in mice (Yazar et al.…”