Insulin action on membrane potential and glucose uptake: Effects of high potassium

These experiments were designed to test the hypothesis that insulin-induced hyperpolarization is a link in the chain of events leading to stimulation of glucose transport. External potassium concentration, [K⁺]₀, was increased by equimolar substitution of KCl for NaCl, a method known to cause cell swelling, and by substitution of [K⁺]₀ for [Na⁺]₀ with maintenance of constant [K⁺]₀. [Cl^-]₀ product, a method that does not cause cell swelling. When there was constant KCl product, even at 76.8 meq [K⁺]₀ insulin continued to hyperpolarize, although by only ~44% as much as in normal [K⁺]₀, and insulin-stimulated 2-deoxyglucose uptake was only ~60% of that at normal [K⁺]₀. With equimolar substitution of KCl for NaCl: 1) electrical potential difference across cell membranes of surface fibers of rat caudofemoralis muscle decreased with logarithm [K⁺]₀, in the presence or absence of insulin. 2) Insulin-induced hyperpolarization decreased as [K⁺]₀ increased and disappeared at 36 mM [K⁺]₀. 3) The amount of insulin bound to its receptors in 1 h was not affected by [K⁺]₀ over the range studied. 4) Insulin effects on membrane potential and on 2-deoxyglucose uptake, as both were altered by [K⁺]₀, correlated well. As the probe moved in depth through the first six fibers there was stepwise decrease in depolarization in high [K⁺]₀ in the absence of insulin. Insulin hyperpolarized the deepest of these fibers, even when it did not hyperpolarize the outermost. The decrease in insulin-induced hyperpolarization as [K⁺]₀ increases is consistent with the hypothesis that insulin hyperpolarizes by decreasing the ratio P(Na)/P(K).