Actions of benzalkonium chloride as a potent depressant at the neuromuscular junction.

Benzalkonium chloride (BA), a positively charged surface active agent, applied (> 10 nM) in the superfusing solution, produced a concentration-dependent reduction in the amplitude of both evoked endplate potentials (EPPs) and spontaneous miniature EPPs of the frog. Voltage-clamped endplate currents (EPCs) and spontaneous miniature endplate currents (MEPCs) were also diminished in amplitude, in the presence of BA (50-140 nM), whereas their time-course and reversal potential were not obviously affected. No significant change due to the addition of 50 nM BA was observed in apparent properties of the ACh channel estimated from ACh-induced current fluctuations. In the relationship between the amplitude of ACh potentials and the net charge for iontophoretic pulses at a single junction, the principal pattern of action of BA (30-60 nM) appeared to be a parallel shift to the right. At concentrations greater than about 1 microM, BA slightly increased the resting input conductance of the non-synaptic muscle fibre membrane. It was suggested that this increase was attributable to a slight increase in Cl ion conductance of the non-synaptic membrane. These results indicate that BA effectively blocked neuromuscular transmission, acting as an ACh receptor antagonist at smaller concentrations and as a more potent blocker that acts through multiple sites at greater concentrations.