Insulin-induced membrane changes in K(+)-depleted rat skeletal muscle.
Insulin-induced membrane changes were investigated in K(+)-depleted rat muscle. Male Sprague-Dawley rats were placed on a K(+)-free but otherwise adequate diet for 5-8 wk; serum K+ concentration ([K+]) dropped to 1.2-3.2 mM. Omohyoid membrane potential was -81 mV in 5.5 mM [K+] (SO4(2-)). Exposure to either insulin or low (0.5 mM) [K+] singly changed potential only slightly. The combination resulted in depolarization of 90% of fibers (-43 mV) and hyperpolarization of 10% of fibers (-101 mV). Fibers from normokalemic rats did not depolarize. Tetrodotoxin (TTX) blocked depolarization, implying the presence of noninactivating TTX-sensitive Na+ channels. K+ currents were measured using the three-electrode voltage clamp; movement of other ions was prevented by ion substitution, channel blockers, and depolarization-induced channel inactivation. K+ conductance was similar in control fibers with or without insulin. In the absence of insulin, currents in K(+)-depleted fibers were offset by a large leakage current that was significantly diminished when insulin was present. The insulin-induced current decrease was observed in nitrendipine, suggesting that the apparent decreased outward current was not an inward current carried by Ca2+. Data are consistent with altered Na+ and K+ channels in K(+)-depleted muscle, i.e., insulin-related closing of K+ channels initiates depolarization, which is then sustained by opening of noninactivating Na+ channels.
Bond
E F
EF
Department of Physiology, University of Washington, Seattle 98195.
Gordon
A M
AM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000502:physiology; D009334:Neck Muscles / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D009568:Nitrendipine / Q000494:pharmacology; D011191:Potassium Deficiency / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007328:Insulin; D013779:Tetrodotoxin; D009568:Nitrendipine