The kinetics of slow muscle acetylcholine‐operated channels in the garter snake.

Abstract

Slow muscle synaptic responses were modeled kinetically in an attempt to define the mechanism by which slow fiber acetylcholine-operated channels differ from those in twitch fibers. Three kinetically distinguishable states were necessary. All applicable 3-state kinetic schemes were considered in an attempt to identify the simplest description of the data. Experimental tests eliminated several models. Two models were not tested because they contained an excessive number of adjustable parameters. The data were not fitted by kinetic schemes which postulated channels which opened with 1 as well as 2 bound agonist molecules, channels which became blocked after opening, or separate populations of synaptic and extrasynaptic channels. The 3-state kinetic model of del Castillo et Katz (1957) accurately described all the data. This sequential model relates a closed channel state with no agonist bound to its receptors, an intermediate state (also closed) with agonist bound, and an open channel state. It is the same model which has been used to describe synaptic responses in twitch fibers. The variation which allows this model to describe both twitch and slow fiber synaptic responses is the lifetime to the intermediate state. In twitch fibers the intermediate state lifetime is undetectably brief by electrophysiological methods. In slow fibers this lifetime appears to be 1-2 ms, varying with voltage. Of the 4 transition rates in this 3-state kinetic scheme, 3 may be estimated by fitting the model to the data. These are the channel opening rate, the channel closing rate and the rate at which closed channels lose their bound agonist molecules. The latter 2 rates appear to depend exponentially on voltage. The channel opening rate was not detectably voltage-sensitive.