Insulin depolarization of skeletal muscle in absence of external Na+.
Three mechanisms have been proposed by which insulin might increase the electrical potential difference across the cell membrane of some of its main target cells: stimulation of an electrogenic pump; increased permeability to K+ (PK); and decreased ratio of permeability to Na+ (PNa) compared to PK, with an absolute decrease in permeability to both ions. Our laboratory has reported that insulin-induced hyperpolarization (IIH) of rat skeletal muscle is not due to stimulation of a ouabain-inhibitable pump and that insulin decreases 42K efflux, apparently eliminating the first two candidate mechanisms. If the remaining hypothesis is correct, when Na+ is removed from the bathing solution, insulin should depolarize, not hyperpolarize. It did. With Tris or N-methyl-D-glucamine substituted for Na+, insulin depolarized by approximately 3 mV. Ouabain had no effect. PNa decreased by greater than 90%; PK was reduced by less than 40%. The main component of the immediate mechanism of IIH is the near elimination of PNa. Furthermore, when a poorly permeable cation was substituted for Na+, muscles hyperpolarized in the absence of insulin. This gave us an opportunity to test the hypothesis that hyperpolarization is a link in the insulin-transduction chain. Consistent with this hypothesis, rat muscles hyperpolarized in this manner in the absence of insulin took up more glucose than paired controls in normal Na+ solution.
Wu
F S
FS
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Rogus
E
E
Zierler
K
K
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism; D006614:Hindlimb; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D014325:Tromethamine / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D007328:Insulin; D014325:Tromethamine; D014634:Valinomycin; D010042:Ouabain; D012964:Sodium; D005947:Glucose; D011188:Potassium