The statistical nature of the acetylcholine potential and its molecular components

Abstract

1. When a steady dose of acetylcholine (ACh) is applied to an end‐plate, the resulting depolarization is accompanied by a significant increase in voltage noise. 2. The characteristic properties of this ACh noise (amplitude and time course) are examined under various experimental conditions. The voltage noise is analysed on the assumption that it arises from statistical fluctuations in reaction rate, and in the frequency of the elementary current pulses (‘shot effects’) produced by the action of ACh molecules. 3. The elementary ACh current pulse (amplitude approximately 10−11 A), arises from a conductance change of the order of 10−10 Ω−1 which lasts for approximately 1 ms (at 20° C), and produces a minute depolarization, of the order of 0·3 μV. It is associated with a net charge transfer of nearly 10−14 C, equivalent to approximately 5 × 104 univalent ions. 4. At low temperature, and during chronic denervation, the duration of the elementary current pulse increases, and the elementary voltage change becomes correspondingly larger. 5. Curare has little or no effect on the characteristics of the elementary event. 6. A comparative study of ACh and carbachol actions shows that carbachol produces considerably briefer, and therefore less effective, current pulses than ACh.

A cyclic‐AMP‐gated conductance in cochlear hair cells

“…It means that the channels are non-selecdivalent cations from the variance-to-mean ratio of the tive which is consistent with the properties of the CAMP-gated current [8], was 16 pS (Ca"', Mg"' free cAMP-gated conductance described here. (2) The solution, holdiag potential -40 mV).…”

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

“…Hence the probability of a channel being open arise if nicotine had some channel blocking activity in was not more than 0.1 and pT(°o) not less than 0.9. respect to the fast channels. Since it is known to act as On these assumptions, lifetimes range from 6.2 ms a cation (Barlow, 1965) voltage relationship for the nicotine-induced inward factor 4.1-5.5 (Katz & Miledi, 1972;Neher & current, comparing it with the curve for carbachol, Sakmann, 1975). The difference between these two which shows no appreciable channel blocking activity agonists is present, but much smaller in the ganglion (Ascher et al, 1979), as described by Adams & cells, the ratio SubCh/CCh being 2.0 for the slow Sakmann (1978a).…”

“…In particular tubocurarine shows strong selectivity in blocking the slow component, whereas hexamethonium more strongly affects the fast component. In this study we have investigated the selectivity of agonists in activating these two components, using the analysis of membrane current noise (Katz & Miledi, 1972; Anderson & Stevens, 1973) to distinguish the contributions of the two types of receptor to the overall membrane response. A noise spectrum consisting of two components can be represented by the equation:…”

“…Where G(f) is the one-sided spectral density GI(O) and G2(0) Katz & Miledi, 1972;Anderson & Stevens, 1973), the noise variance is directly proportional to the mean current, I…”

Decamethonium both opens and blocks endplate channels.

“…ITe voltage dependencies of the channel lifetime and of the blocking equilibrium are similar to those seen with pure agonists and local anesthetics, respectively. The transmitter at the nerve-muscle synapse of vertebrate skeletal muscle, acetylcholine (AcCho), acts by combining with postjunctional receptors and inducing the opening of discrete ion channels (1)(2)(3).A number of other quaternary ammonium compounds mimic this action of acetylcholine, although for some of them the maximum effect is quite feeble. Compounds that produce only small maximum potential or conductance changes are termed partial agonists.…”