Voltage dependence of desensitization. Influence of calcium and activation kinetics.
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 tau, the time constant of desensitization onset, varying as a logarithmic function of membrane voltage. The voltage dependence of tau remained in calcium-deficient solutions and was not altered by elevating either the level of extracellular 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.
D000818:Animals; D001001:Anura; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology*; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D013997:Time Factors
D009467:Neuromuscular Depolarizing Agents; D002217:Carbachol; D011188:Potassium; D002118:Calcium