Abstract
α-Dihydrograyanotoxin II (α-2H-GTX II) is a derivative of the toxic principles from the leaves of various plants of the family Ericaceae. It exerts a potent and reversible depolarizing action on squid axon membranes, the resting membrane potential being eventually reversed in polarity to +5.5 mV. Decrease in external sodium concentration to 1 mM reverses the depolarization. No depolarization is produced by application of α-2H-GTX II when sodium ions are absent from both external and internal media. It is concluded that a specific increase in resting sodium permeability is responsible for the depolarization of the nerve membrane by α-2H-GTX II. The dose-response curve is fitted by one-to-one stoichiometry for the interaction between the toxin and the receptor, and the concentrations required for half-maximum depolarization are estimated to be 2.61 x 10-6 and 2.63 x 10-6 M for external and internal applications, respectively. When applied externally, tetrodotoxin antagonizes the depolarization caused by external or internal application of α-2H-GTX II in a mixed, competitive and noncompetitive manner. Externally applied procaine or benzocaine partially antagonizes the depolarization by α-2H-GTX II. The sodium activation and inactivation mechanisms are unaffected by 1 x 10-6 M α-2H-GTX II, whereas the potassium activation mechanism is inhibited by 22%. β-Dihydrograyanotoxin II has little or no effect on the resting membrane potential and membrane currents. Lyoniol A has no effect on the resting membrane potential.
Footnotes
- Received May 10, 1972.
- Accepted October 2, 1972.
- © 1973 by The Williams & Wilkins Co.
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