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

1. Slow muscle synaptic responses were modelled kinetically in an attempt to define the mechanism by which slow fibre acetylcholine-operated channels differ from those in twitch fibres. 2. Three kinetically distinguishable states were necessary. 3. All applicable three-state kinetic schemes were considered in an attempt to identify the simplest description of the data. Experimental tets eliminated several models. Two models were not tested because they contained an excessive number of adjustable parameters. 4. The data were not fitted by kinetic schemes which postulated (i) channels which opened with one as well as two bound agonist molecules, (ii) channels which became blocked after opening, or (iii) separate populations of synaptic and extrasynaptic channels. 5. The three-state kinetic model of del Castillo & 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 fibres. 6. The variation which allows this model to describe both twitch and slow fibre synaptic responses is the lifetime of the intermediate state. In twitch fibres the intermediate state lifetime is undetectably brief by electrophysiological methods. However, in slow fibres this lifetime appears to be 1-2 msec, varying with voltage. 7. Three of the four transition rates in this three-state kinetic scheme 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 two rates appear to depend exponentially on voltage. The channel opening rate was not detectably voltage-sensitive.