Blockage of Sodium Conductance Increase in Lobster Giant Axon by Tarichatoxin (Tetrodotoxin)

Abstract

A~STRACT Tarichatoxin, isolated from California newt eggs, has been found to selectively block the increase of sodium conductance associated with excitation in lobster giant axons at nanomolar concentrations. This resulted from a reduction in the amplitude of the conductance increase rather than a change in its temporal characteristics. The normal potassium conductance increase with depolarization is not altered. A high concentration of calcium applied concomitantly with the toxin significantly improves the reversibility of the sodium blocking. This toxin has recently been identified as chemically identical with tetrodotoxin from the puffer fish. Toxins from the two sources are equally effective and are shown to have an action which is distinctly different from that of procaine.

Comparison of Tetrodotoxin and Procaine in Internally Perfused Squid Giant Axons

“…The gate is probably controlled by membrane potential and calcium (Goldman, 1964). High external calcium concentration has been shown to interact with the blocking action of T T X (Takata et al, 1966), and this is consistent with the above mentioned notion.…”

“…Procaine differs from T T X not only in this nonselective blockage but also in its much higher threshold concentration and its effect on the kinetics of the early transient conductance increase (Takata et al, 1966).…”

“…Procaine differs from T T X not only in this nonselective blockage but also in its much higher threshold concentration and its effect on the kinetics of the early transient conductance increase (Takata et al, 1966). In the meantime the internal perfusion technique has been developed for squid axons (Baker, Hodgkin, and Shaw, 1961; Oikawa, Spyropoulos, Tasaki, and Teorell, 1961), giving us a straightforward approach for study of symmetry or asymmetry of the nerve membrane with respect to the action of various agents (Narahashi, 1963(Narahashi, , 1965 Baker, Hodgkin, and Shaw, 1962; Tasaki, Watanabe, and Takenaka, 1962; Tasaki and Takenaka, 1964;Rojas, 1965).…”

Barbiturates Block Sodium and Potassium Conductance Increases in Voltage-Clamped Lobster Axons

“…This steady hyperpolarization (lobster axon resting potentials average about -7 0 mv in the absence of a sucrose gap) which normally occurs under a sucrose gap (Julian et al, 1962 a;Blaustein and Goldman, 1966 b) may be expected to minimize resting sodium inactivation. Takata et al (1966, Fig. 4) have shown that in the lobster giant axon under a sucrose gap, the resting sodium inactivation in normal artificial seawater is negligible at holding potentials greater than -100 m y .…”

Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity

“…To develop additional evidence that inhibition of Na + currents is the likely mechanism of action we also studied riluzole, an agent approved for the treatment of ALS, which has been shown to also inhibit voltage-dependent Na + channels, [20][21][22] and tetrodotoxin, a poison from the puffer fish that is highly specific for voltage-gated Na + channels. 23,24 Finally, we were interested in whether other AEDs could also protect against NRHypo neurotoxicity. We, therefore, studied felbamate and gabapentin, two AEDs whose mechanism of action is less clear, 25 as well as ethosuximide, an AED which is not known to interact with voltage-gated Na + channels but instead inhibits the low threshold type of transient calcium current (T-type current).…”