Sub-nanomolar concentrations of ciguatoxin-1 excite preganglionic terminals in guinea pig sympathetic ganglia

Abstract

The actions of low concentrations of ciguatoxin-1 (CTX-1, 0.2-0.8 nM) in guinea-pig sympathetic ganglia have been analysed using intracellular recording techniques in vitro. The effects of CTX-1 were graded with concentration but sensitivity varied markedly between neurones in the same preparation. Other than an initial transient (approximately 10 min) depolarization of some ganglion cells accompanied by an increase in input resistance, passive electrical properties did not significantly differ from controls. Amplitude and threshold of action potentials evoked by depolarizing current and threshold, latency and form of the initial responses to nerve stimulation were also not affected. Exposure to CTX-1 generated marked increases in the frequency of spontaneous excitatory synaptic potentials which often occurred in bursts (15-66 Hz) of similar amplitudes. Single stimuli to incoming nerves produced repetitive synaptic responses arising from preganglionic, but not from peripheral afferent, axons. Following brief (< 5 min) exposure to CTX-1, these effects declined over 30 min but, after longer exposure (> 15 min), they persisted for several hours despite continuous washing. All activity generated by CTX-1 was significantly reduced or abolished by d-tubocurarine (10(-5)-10(-4) M), hexamethonium (10(-5) M), tetrodotoxin (10(-7)-10(-6) M), omega-conotoxin (10(-7) M), reduced Ca2+ (0.1 mM)/raised Mg2+ (10 mM), raised Ca2+ (6 mM) or raised Mg2+ (25 mM). The data suggest that CTX-1 activates preganglionic axons by modifying the voltage sensitivity of a subpopulation of Na+ channels. Effects on these unmyelinated axons occur at much lower concentrations than have been reported to affect myelinated ones. Many of the symptoms of ciguatera poisoning might be explained by activity in autonomic and perhaps other unmyelinated nerve terminals.