Mechanism of nerve membrane depolarization caused by grayanotoxin I

Abstract

SUMMARY1. 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 mmw.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 106 cm/sec by internal application of 1 x 10-5 M arayanotoxin 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 412 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.

FURTHER EVIDENCE FOR THE INVOLVEMENT OF Na+CHANNELS IN THE RELEASE OF ADRENAL CATECHOLAMINE: THE EFFECT OF SCORPION VENOM AND GRAYANOTOXIN I

“…Like veratridine (Ito et al, 1978;, scorpion venom and grayanotoxin I plus scorpion venom caused an increase in the catecholamine output from the perfused adrenal gland in the presence of atropine and hexamethonium and the effects were blocked by TTX or by deprivation of extracellular Na+ or Ca2+ ions. These neurotoxins are known to act on TTX-sensitive Na+ channels in various excitable cells (Narahashi et al, 1972;Ohta et al, 1973;Narahashi & Seyama 1974;Starkus & Narahashi 1978), although the mechanism of action is somewhat different. In addition, these toxins failed to depolarize the nerve axons in the absence of or in low extracellular Na+ (Adam et al, 1966;Narahashi & Seyama 1974;Starkus & Narahashi 1978).…”

“…Inhibitory effect of tetrodotoxin on catecholamine secretion induced by scorpion venom and grayanotoxin I It is reported that either TTX or reduction of extracellular Na+ ions abolishes the depolarization or the prolongation of Na+ current induced by grayanotoxin I and/or scorpion venom in various excitable cells (Adam et al, 1966;Narahashi et al, 1972;Narahashi & Seyama 1974;Starkus & Narahashi 1978). Scorpion toxin-induced release of noradrenaline from peripheral adrenergic neurones is also inhibited by Adrenal glands were first perfused with Ca2 +-free solution containing Mg2 + 2 mM for 25 min.…”

“…Scorpion venom (Adam, Schmidt, Stampfli & Weiss, 1966;Narahashi, Shapiro, Deguchi, Scuka & Wang, 1972) and grayanotoxin (Narahashi & Seyama, 1974;Starkus & Narahashi, 1978) like veratridine (Ohta, Narahashi & Keeler, 1973) are known to activate tetrodotoxin-sensitive Na+ channels in various neuronal tissues. Therefore, both scorpion venom and grayanotoxin may provide further evidence for the involvement of Na+ channels in adrenal catecholamine secretion.…”

Mad Honey Poisoning: A Review

“…Grayanotoxin binds the voltage-dependent sodium (Na) channel of excitable cells from the inside of the cell [16] in its open state [17]. The receptor consists of the S6 transmembrane segments of four homologous domains facing the ionconducting pore [18].…”

Effect of Crotamine, a Toxin of South American Rattlesnake Venom, on the Sodium Channel of Murine Skeletal Muscle

“…In order to see whether the antagonistic effect of high concentrations of K+ was due simply to the reduced membrane potential, the effect of grayanotoxin I (Seyama, 1970;Narahashi & Seyama, 1974), was studied. In confirmation of previous reports, grayanotoxin I at 5 gig/ml depolarized the rat diaphragm muscle from -83 mV to about -50 mV in about 20 min and the effect did not increase.…”