N-ethylmaleimide effects on synaptic transmission in frog sympathetic ganglion

In the isolated bullfrog sympathetic ganglion N-ethylmaleimide (NEM) produced time- and concentration-dependent effects that were irreversible by bathing in drug-free Ringer's solution. Initially, synaptic transmission was facilitated; this was evident as augmented action potential amplitude, repetitive synaptic firing and partial reversal of low [Ca++] transmission failure. Subsequently, transmission was depressed progressively to the point of complete block. Conduction in B and C fiber groups of the preganglionic nerve trunk was also blocked by NEM, without initial facilitation, but at a rate slower than the block of synaptic transmission. NEM had no effect on the amplitude of ganglion cell membrane depolarization produced by acetylcholine, suggesting that its effects were not exerted on postsynaptic nicotinic receptors. None of the effects of NEM were produced by the saturated analog N-ethylsuccinimide. Facilitatory effects of NEM may be attributable to inhibition of Na+ inactivation, or to increased entry of Ca++, at presynaptic nerve terminals. Because the late depressant stages of NEM action involve multiple sites (presynaptic, postsynaptic and axonal), the clarification of possible mechanisms will be a difficult experimental problem.