Tetrodotoxin affects sodium gating current in squid giant axon
Molecular rearrangements of the sodium channels associated with membrane depolarization can be electrophysiologically studied by the analysis of the single-channel records or, more directly, by measurements of the gating current. Since the gating charge movement reflects the transition of the channel between protein conformations that include all the closed and the open state(s), the movement provides information which cannot be obtained as readily from macroscopic ionic currents or single-channel records. Tetrodotoxin (TTX), a cationic toxin that specifically blocks the sodium current, has long been believed to plug the ion-selective filter without any significant effect on the gate current. The guanidinium group of TTX is thought to bind to the charge of the filter in particular. However, several experiments have demonstrated that TTX (or STX) does affect sodium channel gating. The present chapter compares sodium gating currents of giant axons of squid in the presence and absence of external TTX. In contrast to the lack of effect previously reported for squid giant axons, significant effects of TTX on sodium gating currents are noted. This chapter also provides experimental evidence that TTX binds to the gating site of the sodium channel in the squid giant axon to inhibit the transition primarily between the final closed state and the open state.
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