Voltage dependence of desensitization to carbamylcholine in frog muscle fibers reverses in low-calcium solutions

Abstract

1. The effect of reduction in external Ca concentration on the voltage dependence of desensitization to carbamylcholine was studied in frog muscle fibers to determine whether local increase in cytosolic free Ca2+ from inward movement through agonist-activated receptor channels is a factor producing increased desensitization rate, as has been proposed. A critical feature is whether or not the relation of desensitization rate with voltage decreases in a regular manner as potential is increased to levels above ECa. 2. A conventional two-electrode voltage clamp procedure was used for voltage control of the postjunctional membrane of K-depolarized muscle fibers, and a standard 1-mM solution of carbamylcholine was applied to voltage-clamped endplates by local superperfusion from a micropipette. Measurements of average sarcomere length were also made in separate experiments to detect persistent raised levels of internal Ca2+ in the high-K test media. 3. In high-K test solutions containing 1.8 mM Ca, desensitization rate decreased in a regular monotonic relation with increase in potential through the range from -40 to +30 mV, giving an exponential voltage sensitivity factor of 0.016 mV-1. 4. By contrast, desensitization onset rate in high-K test media containing Ca ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (CaEGTA) buffer (calculated free Ca2+ = 61 nM) showed a nonmonotonic, reversing relation with potential characterized by a decrease in rate between -40 and -20 mV and an increase of rate with increase in potential from -20 to +30 mV.(ABSTRACT TRUNCATED AT 250 WORDS)