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

Abstract

SUMMARY1. 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 tests 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.

Analysis of current noise evoked by nicotinic agonists in rat submandibular ganglion neurones

“…Before accepting the first conclusion it is necessary to be sure that it does not represent an artefact of the fitting procedure. This is made unlikely by the fact that the estimated half power frequen- Adams, 1977;Ascher, Marty & Neild, 1978b;Ascher et al, 1979;Dionne, 1981). No such effects on either f,,, or the half power frequencies were observed here for any of the agonists, including nicotine.…”

Acetylcholine receptor channels and their block by clonidine in cultured bovine chromaffin cells.

“…for one and two Lorentzian fits, respectively; where G(0), G,(O) and G2(0) are the zero frequency asymptotes and f, fc1 and fL2 their half-power frequencies (see Dreyer, Walther & Peper, 1976;Dionne, 1981). There was always good agreement between the two methods.…”

Paired Motor Neuron–Muscle Recordings in Zebrafish Test the Receptor Blockade Model for Shaping Synaptic Current

“…This blocking model has been subsequently proposed for even well characterized neuromuscular synapses such as those in frogs and mammals (Legendre et al, 2000). The ability of ACh to block the ACh receptor channel under experimental conditions is well documented (Sine and Steinbach, 1984;Ogden and Colquhoun, 1985;Liu and Dilger, 1991;Maconochie and Steinbach, 1995), but there has been no direct evidence supporting involvement of ACh block during synaptic transmission (Dionne, 1981). Moreover, the concentration of transmitter required for effective channel block is approximately two orders of magnitude greater than the concentration required to activate ACh receptors, representing a much higher concentration than thought to actually occur at the neuromuscular junction.…”