Delay of desensitization onset by potassium ion in voltage-clamped frog muscle fibers.

Increase in extracellular K+ concentration causes delay in desensitization onset during prolonged application of carbamylcholine to the postjunctional membrane in muscle. This could be due to a direct action of K+ on acetylcholine receptors or to some change in the receptors related to K+-induced effects on transmembrane potential. The question of direct vs. voltage-dependent action of K+ was investigated in frog muscle (Rana pipiens) using a point-source voltage clamp. In conductance measurements first without voltage control, desensitization rate in bath media containing 33 mM K+ was -0.198 s-1 among fibers showing an average potential of -30 mV and -0.104 s-1 in 165 mM K+ where the average potential was -2 mV, a decrease of 47%. By comparison, in voltage-clamp tests at a nominal holding potential of +20 mV, increasing extracellular K+ from 33 to 165 mM caused a decrease of 61% in desensitization rate from -0.151 to -0.059 s-1. Another series in 165 mM K+ at a holding level of +10 mV showed a decrease of 67% to a rate of 0.047 s-1. It is concluded that increases in extracellular K+ can delay desensitization onset independently of effects on transmembrane potential. It is suggested that this could result from a direct interaction of K+ with sites on the outer receptor moiety or within channels, but probably not at the inner membrane face, if the latter are considered in equilibrium with bulk intracellular K+.