Endplate channel actions of a hemicholinium-3 analog, DMAE.

The effect of the hemicholinium-3 analog, DMAE, on endplate currents (EPC) was investigated in the transected cutaneous pectoris muscle of the frog using a conventional two-microelectrode voltage clamp. At a low concentration (5 microM), DMAE produced a long-lasting decrease in the rate constant of decay (alpha) and an increase in the peak current amplitude (Ip). At higher concentrations (10--100 microM), DMAE produced biphasic changes characterized by a transient, marked decrease of alpha and increase of Ip followed by a long-lasting marked increase of alpha and decrease of Ip. When DMAE was removed from the bath recovery from block was asymmetrical in that alpha recovered more quickly than did Ip. Pretreatment with neostigmine or collagenase partially antagonized the initial effects without affecting the steady state effects of DMAE, indicating that the initial effects of DMAE may be, at least in part, due to inhibition of the enzyme acetylcholinesterase. The drug reverses the normal voltage dependence of alpha without altering the single exponential nature of decay of the EPC. The inward EPC was more markedly blocked than outward EPC, resulting in a highly non-linear current-voltage relation with Ip decreasing with increasing hyperpolarization. This effect may indicate that DMAE causes a voltage-dependent block of closed acetylcholine-activated ion channels.