Mechanism of nerve membrane depolarization caused by grayanotoxin I.
1. The mechanism of depolarization of squid axon membranes caused by grayanotoxin I has been studied by means of internal perfusion and voltage clamp techniques.2. The depolarization induced by either internal or external application of grayanotoxin I was reversed by decreasing the external sodium concentration from 449 to 1 mm.3. No depolarization was observed when both external and internal media were devoid of sodium ions, indicating that the depolarization by grayanotoxin I in normal media is due to a specific increase in resting sodium permeability.4. The resting sodium permeability as measured by voltage clamp was increased to 1.31 x 10(-6) cm/sec by internal application of 1 x 10(-5)m grayanotoxin I, an increase by a factor of about 90.5. The apparent dissociation constant of internally applied grayanotoxin I in increasing the resting sodium permeability was estimated to be 4.12 x 10(-5)m, and the toxin interacts with the membrane receptor on a one-to-one stoichiometric basis.6. Tetrodotoxin antagonized the action of grayanotoxin I in increasing the resting sodium permeability in a non-competitive manner.
D000818:Animals; D000992:Antitoxins; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D003470:Culture Media; D049832:Decapodiformes; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010936:Plant Extracts; D010944:Plants; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology*
D000992:Antitoxins; D003470:Culture Media; D004224:Diterpenes; D009467:Neuromuscular Depolarizing Agents; D010936:Plant Extracts; D014118:Toxins, Biological; D013779:Tetrodotoxin; D012964:Sodium; C001311:grayanotoxin I