Ciguatoxin-induced oscillations in membrane potential and action potential firing in rat parasympathetic neurons
The actions of ciguatoxins from the Pacific (P-CTX-1) and Caribbean (C-CTX-1) regions were investigated in isolated parasympathetic neurons from rat intracardiac ganglia using patch-clamp recording techniques. Under current-clamp conditions, bath application of P-CTX-1 (1-10 nM) or C-CTX-1 (10-30 nM) caused a gradual depolarization that was accompanied by oscillation of the membrane potential leading to tonic action potential firing. Membrane potential oscillations were observed between -45 and -60 mV and had an amplitude of 10-20 mV and a mean frequency of 10 Hz. Oscillation frequency was temperature-dependent with a Q10 of 2.0. Membrane oscillations were temporarily inhibited by hyperpolarizing current pulses and potentiated by weak depolarizing current pulses. The amplitude of oscillations was reduced upon lowering the external Na+ concentration and inhibited by tetrodotoxin (TTX), tetracaine or Zn2+. Tetraethylammonium, 4-aminopyridine, Cs+, Cd2+, Ba2+, 1,4,4′-diothiocyanato-2,2′-stilbenedisulphonic acid (DIDS) and ouabain had no effect on the CTX-1-induced membrane depolarization and oscillations. Brevetoxin (PbTx-3, 100 nM), in contrast to CTX-1, caused a membrane depolarization that was not associated with oscillation of the membrane potential. Under voltage-clamp conditions, P-CTX-1 inhibited the peak amplitude of the voltage-dependent Na+ current and shifted the activation curve to more negative potentials, but membrane oscillations were not seen in this configuration. These results suggest that ciguatoxins cause oscillation of the membrane potential in mammalian autonomic neurons by modifying the activation and inactivation properties of a population of TTX-sensitive Na+ channels.