Ciguatoxin (CTX-1) modulates single tetrodotoxin-sensitive sodium channels in rat parasympathetic neurones.
The actions of the marine neurotoxin, ciguatoxin-1 (CTX-1), were investigated in isolated parasympathetic neurones from neonatal rat intracardiac ganglia using patch-clamp recording techniques. Under current clamp conditions, bath application of 1-10 nM CTX-1 caused gradual membrane depolarization and tonic action potential firing. Action potential firing ceased with depolarization beyond approximately -35 mV and application of 300 nM tetrodotoxin (TTX) repolarized the cell to its control resting potential. In cell-attached membrane patches, 1-10 nM CTX-1 in the patch pipette markedly increased the open probability of single TTX-sensitive Na+ channels in response to depolarizing voltage steps but did not alter the unitary conductance (10 pS) or reversal potential. Under steady-state conditions, CTX-1 caused spontaneous opening of single Na+ channels which did not inactivate at hyperpolarized membrane potentials. CTX-1 increases neuronal excitability by shifting the voltage of activation of TTX-sensitive Na+ channels to more negative potentials.
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
R C
RC
Hogg
R J
RJ
Lewis
D J
DJ
Adams
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002922:Ciguatoxins / Q000494:pharmacology*; D004553:Electric Conductivity; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D015222:Sodium Channels; D002922:Ciguatoxins; D013779:Tetrodotoxin