Rate of action of Anemonia sulcata toxin II on sodium channels in myelinated nerve fibres.

1. The effect of Anemonia sulcata toxin II (ATX II) on single myelinated nerve fibres of the frog, Rana esculenta, was investigated. 2. ATX II promptly and reversibly increased the duration of action potentials; on applying 9.5 micro M the time, t0.5, to reach half of the final effect was 2.6 s. In the presence of 10 mM tetraethylammonium the duration was very sensitive to ATX II and as little as 10 nM could be detected. 3. The underlying mechanism was a diphasic incomplete inactivation of sodium channels which, at 15 degrees C, caused a sizeable INa to persist after 15 ms depolarization (I15ms). 4. On applying 5 micro M (1.25 micro M) ATX II at ca. 15 degrees C, I15ms developed with a sigmoid time course whose t0.5 was 1.5 s (2.6 s) and on washing declined in a near-exponential fashion with tau off = 6.1 s (6.4 s). Washing after a short (1-2s) application led to a transient considerable increase in I15ms followed by a faster decline with tau'off less than tau off. 5. Cooling decreased the rate of action with a Q10 of 1/tau0.5 = 1.9 and of 1/tau off = 2.0 (between 7 and 14 degrees C). ATX I (up to 15 micro M) was ineffective and did not antagonize ATX II. 6. Both rates of diffusional access and reaction seem to contribute to the rate of action. The results suggest a superficial binding site.