Insulin stimulation of an electrogenic pump at high extracellular potassium concentration.

There is no agreement about the immediate mechanism by which insulin hyperpolarizes skeletal muscle, adipocytes, and myocardium. Of three candidates, one has been eliminated; the hyperpolarization is not secondary to an increase in intracellular [K]. There are reports that insulin hyperpolarizes by increasing relative permeability to K compared with that to Na ions, and other reports that insulin stimulates an ouabain-sensitive electrogenic Na-K exchange pump. Our evidence has been interpreted to support the former and deny the latter, when rat skeletal muscle is bathed at normal [K]. Crucial evidence for the latter has not been reported: insulin hyperpolarizes to a potential more negative than the K equilibrium potential. We now report that when rat caudofemoralis muscle is incubated with insulin at normal extracellular [K], then depolarized by increasing extracellular [K] to 38.4 mM, by equimolar substitution of KCl for NaCl, there is hyperpolarization compared with potentials of muscles treated similarly with respect to [K] but without insulin. Under these circumstances, the membrane potential in the presence of insulin is more negative than the new K equilibrium potential, and, in contrast to our previous experience with muscles bathed only in normal [K], the hyperpolarization in high [K] is reduced or eliminated by ouabain.