Ethanol reduces excitatory postsynaptic current duration at a crustacean neuromuscular junction

Abstract

ETHANOL potentiates the postsynaptic voltage response to acetylcholine at mammalian and amphibian neuromuscular junctions^1–4, by prolonging the duration of the postsynaptic conductance change^5–7. At these synapses, hyperpolarisation also increases the time constant of decay (τ) of end-plate currents^8–14. Because of this voltage sensitivity, it was proposed¹⁵ that the rate-limiting reaction in the decay of end-plate currents involves the relaxation of membrane proteins, which undergo a change in dipole moment normal to the field direction as they change conformation. The magnitude and direction of the change in dipole moment then determines the effect of electric field on α, the reaction rate, α ( = τ⁻¹) would be proportional to exp (Vμ) (ref. 15) where V is membrane potential and μ the dipole moment change normal to the field direction. It has been suggested that the prolonged decay of end-plate currents produced by ethanol is due to increase by ethanol of the dielectric constant of the environment of receptors⁶, which lowers the rate of reactions involving a decrease in dipole moment¹⁶ and hence increases τ. In some arthropods, including crayfish, crab and locust, there is evidence that glutamate acts as an excitatory transmitter at neuromuscular junctions^17,18. Also, the decay of excitatory postsynaptic currents in crayfish¹⁹ and locusts²⁰ has the opposite voltage sensitivity to that found at amphibian neuromuscular junctions: hyper-polarisation reduces τ, suggesting that the rate-limiting reaction in the decay of conductance at these ‘glutamate’ synapses could be associated with a change in dipole moment which is opposite to that seen at amphibian neuromuscular junctions. Ethanol could then have an opposite effect at these two types of synapse, and depress synaptic transmission at glutamate synapses. We report here results of our study of spontaneous miniature excitatory junctional currents (MEJCs) in the crab, which confirm this hypothesis.