Decamethonium both opens and blocks endplate channels

Abstract

Miniature endplate currents, endplate current fluctuations ('membrane noise'), and voltage-jump current relaxations were studied in voltage-clamped frog muscle fibers during decamethonium action. All three types of experiments revealed two kinetic processes controlling the opening of end-plate channels, one that reflects agonist action and another that reflects local anesthetic-like blocking activity. The kinetic constants for these two steps were evaluated from measurements of the fast and slow time constants as a function of decamethonium concentration. At -130 mV membrane potential and 13°, the mean open time of decamethonium-activated channels is 2.8 msec. The forward and backward rate constants for channel blocking are 1.7 x 107 M-1 sec-1 and 103 sec-1. The voltage dependencies of the channel lifetime and of the blocking equilibrium are similar to those seen with pure agonists and local anesthetics, respectively.