Effects of some aliphatic alcohols on the conductance change caused by a quantum of acetylcholine at the toad end-plate.

1. The post-synaptic effects of the aliphatic alcohols, ethanol to hexanol, were investigated at the neuromuscular junctions of toads, with particular emphasis on the effects of ethanol. 2. The alcohols increased the amplitude and duration of miniature end-plate potentials. It is shown that this effect was due to the prolongation of the decay phase of miniature end-plate currents (m.e.p.c.s). There was no effect of alcohols on the growth phase of m.e.p.c.s. 3. The prolonged decay of m.e.p.c.s in ethanol remained exponential and was normally sensitive to membrane potential. Prolonged m.e.p.c.s were associated with an equivalent prolongation of the mean duration of elementary events, as determined from power spectra of acetylcholine noise in 0-5 M ethanol. 4. The relationship betweeen the time constant of decay of m.e.p.c.s (tau) and the concentration of an alcohol of carbon chain length N (C-N) was exponential, conforming to the equation tau equals tau-s exp (B-N-C-N), in which tau-s is the decay time constant in standard solution and B-N is a constant, different for each alcohol. 5. There was also an exponential relationship between B-N and N, which closely followed the relationship between membrane-buffer partition coefficient and carbon chain length for the different alcohols, indicating that the alcohols are active in the lipid phase of the post-synaptic membrane. 6. It is suggested that the alcohols act by causing a change in the dielectric constant of the post-synaptic membrane which forms the environment of the rate-limiting reaction responsible for the decay of the end-plate conductance. On the assumption that this reaction involves dipoles, it is shown that the small changes in dielectric constant, calculated from the partition coefficients of the alcohols and by assuming an initial lipid dielectric constant of 3, would give an exponential relationship between the time constant of decay of m.e.p.c.s and alcohol concentration. 7. The results support the hypothesis that the decay (but not the onset) of acetylcholine-induced conductance changes is rate-limited by a first-order reaction which involves dipoles and occurs in the lipid environment of the post-synaptic membrane.