Mechanism of nerve membrane depolarization caused by grayanotoxin I

Abstract

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.