Nicotinic receptors of frog ganglia resemble pharmacologically those of skeletal muscle

Abstract

The actions of ACh antagonists were studied on synaptic currents of autonomic ganglia of the frog. Fast excitatory synaptic currents (ESCs) were recorded from cardiac and paravertebral neurons with the use of the 2-microelectrode voltage-clamp method. The actions of 4 ACh antagonists, tubocurarine, hexamethonium, trimetaphan, and decamethonium were studied. Tubocurarine was effective at reducing the peak amplitude of ESCs (50% inhibition at 3 μM). In contrast, tubocurarine (1-30 μM) reduced the time constant of ESC decay by only 9% compared with controls. Both of these effects of tubocurarine were independent of membrane potential. Hexamethonium was a weak inhibitor of ESCs; at 600 μM peak amplitude was reduced only to about 60% of controls and decay time constants were unaffected at concentrations between 10 and 600 μM. These effects of tubocurarine and hexamethonium are consistent with these drugs being receptor antagonists with no evidence of ion channel block. Trimetaphan (3-100 μM) and decamethonium (100 μM) reduced the peak amplitude of ESCs. In the presence of 100 μM trimetaphan or 10 μM decamethonium, ESC decays were biexponential. The 2 exponential components induced by the presence of these drugs were faster and slower, respectively, than the single-exponential component of control ESC decays. The effects of these 2 drugs were more pronounced at hyerpolarized potentials and are consistent with a channel-blocking action. The actions of the 4 ACh antagonists on frog autonomic ganglia are similar to their effects at the neuromuscular junction but dissimilar to their effects on the rat submandibular ganglion. We conclude that the ACh receptor-ion channel complex present on ganglia on the frog is pharmacologically similar to that at the end-plate and represents a distinct class of neuronal nicotinic receptor responsible for mediating fast excitatory transmission.