Thiamine blockade of neuromuscular transmission

The effects of thiamine on neuromuscular transmission were studied. Thiamine (0.2-2 mM) decreased the quantal height (q) of the evoked end-plate current (EPC). In the presence of 2 mM thiamine, the shape of the decay phase of the EPC remained exponential but the decay time constant increased dramatically. Thiamine changed the EPC height/holding potential and log (EPC decay time constant)/holding potential relationships from linear to non-linear. The reversal potential and the rate of rise of the EPC were unaffected. Analysis of the ACh-induced noise revealed that thiamine increased the mean channel lifetime and decreased the single channel conductance. Under normal conditions, the ACh-induced single channel conductance had no membrane voltage dependency, while thiamine caused the single channel conductance to decrease with hyperpolarization. The effects of thiamine could be explained in computer simulation of the peak EPC/membrane potential relationship by the assumption that thiamine prolonged the channel lifetime and decreased the single channel conductance with hyperpolarization. It is concluded that thiamine modifies the kinetics of ACh-receptor ion channel complex and that this effect is dependent on the membrane voltage.