Modulation of transmembrane potential of isolated cardiac myocytes by insulin and isoproterenol.
Isolated muscle cells from adult rat heart have been used to study the effects of insulin and catecholamines on transmembrane potential by following triphenylmethylphosphonium cation uptake. Insulin was found to hyperpolarize the cells with a maximal effect of 3.2 +/- 0.7 mV (n = 4) at an insulin concentration of 3 x 10(-9) mol/l. This insulin action was fully antagonized by isoproterenol (10(-5) mol/l), which depolarized the cardiocytes in a dose-dependent fashion with a maximal effect of 9.5 +/- 2.2 mV. Treatment of cardiocytes with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or CsCl resulted in a total loss of insulin action, whereas isoproterenol action was not affected. Cardiac myocytes from streptozotocin diabetic rats exhibited an unaltered hyperpolarization by insulin within the physiological concentration range. Isoproterenol now induced a biphasic response with a significant hyperpolarization at low doses and a decreased depolarization at maximal concentrations. In conclusion, 1) hormonal modulation of cardiac myocyte membrane potentials involves hyperpolarization by insulin and depolarization by beta-agonists, 2) insulin action appears to be related to an increased potassium conductance and may be antagonized by beta-stimulation, and 3) membrane potential modulation may be profoundly altered in the diabetic state.
Diabetes Research Institute, Düsseldorf, Federal Republic of Germany.
J
J
Eckel
H
H
Reinauer
D000818:Animals; D001696:Biomechanical Phenomena; D002395:Catecholamines / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004594:Electrophysiology; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D007328:Insulin; D007545:Isoproterenol