Voltage dependence of desensitization. Influence of calcium and activation kinetics.

Abstract

The voltage dependence of carbachol-induced desensitization has been analyzed in K depolarized frog sartorius muscle preparations with voltage clamp techniques over a wide voltage range (-120 to +40 mV). Desensitization developed exponentially at all voltages with .tau., the time constant of desensitization onset, varying as a logarithmic function of membrane voltage. The voltage dependence of .tau. remained in Ca-deficient solutions and was not altered by elevating either the level of extracellular or intracellular Ca. Results according to a simple sequential kinetic scheme in which the rate-limiting step in the development of desensitization is a transition of the receptor channel complex from the activated conducting state to a desensitized, nonconducting state. The observed voltage sensitivity of desensitization primarily resides in the voltage dependence of this transition and the kinetics of activation appear to have a greater influence on the observed rate of desensitization than on its voltage dpendence. A greater change in free energy is required for the transition to the desensitized state than for the transition between the open and closed states of the receptor channel complex.