A B S T R A C T The voltage dependence of carbachol-induced desensitization has been analyzed in potassium-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 % the time constant of desensitization onset, varying as a logarithmic function of membrane voltage. The voltage dependence of r remained in calcium-deficient solutions and was not altered by elevating either the level of extraeellular or intracellular calcium. We have analyzed our 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. We conclude (a) that the observed voltage sensitivity of desensitization primarily resides in the voltage dependence of this transition, and (b) the kinetics of activation appear to have a greater influence on the observed rate of desensitization than on its voltage dependence. The magnitude of the voltage dependence suggests that 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.
The time course of carbachol-induced desensitization onset and recovery of sensitivity after desensitization have been compared at the frog neuromuscular junction. The activation-desensitization sequence was determined from input conductance measurements using potassium-depolarized muscle preparations. Both desensitization onset and recovery from desensitization could be adequately described by single time constant expressions, with Tonset being considerably shorter than ~'~overy. In nine experiments, ronset was 13 --+ 1.3 s and r~overy was 424 -+ 51 s with 1 mM carbachol. Elevating the external calcium or carbachol concentration accelerated desensitization onset without changing the recovery of sensitivity after equilibrium desensitization. Desensitization onset was accelerated by a prior activation-desensitization sequence to an extent determined by the recovery interval that followed the initial carbachol application. The time course of return of ~'0n~t was closely parallel to, but slower than the time course of recovery of sensitivity. These results are consistent with a cyclic model in which intracellular calcium is a factor controlling the rate of development of desensitization.
A B S T R A C T The influence of voltage on the time-course of desensitization onset and recovery has been studied at the frog neuromuscular junction. The activationdesensitization sequence was determined from carbachol-induced end-plate currents in potassium-depolarized fibers voltage-clamped either to -40 mV or +40 mV. The time-course of both desensitization onset and recovery developed exponentially, with onset occurring more rapidly than recovery. Desensitization onset was voltage dependent, the onset time constant being 8.3 -+ 1.3 s (11 fibers) at -40 mV and 19.3 -+ 3.4 s (15 fibers) at +40 mV. Recovery from desensitization was also influenced by voltage. The extent of recovery after 2 min was 80.4 -+ 6.3% in those fibers voltage-clamped to -40 mV and 57.4 -+ 3.6% in those fibers voltageclamped to +40 mV. The voltage dependence of desensitization onset and recovery did not result from a difference in ability to control voltage at these two levels of membrane potential. These results demonstrate that in the potassium-depolarized preparation the processes controlling both desensitization onset and recovery of sensitivity from the desensitized state are influenced by membrane voltage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.