Inhibition of the collapse of the Shaker K+ conductance by specific scorpion toxins

The Shaker B K+ conductance (G(k)) collapses when the channels are closed (deactivated) in Na+ solutions that lack K+ ions. Also, it is known that external TEA (TEA(o)) impedes the collapse of G(k) (Gomez-Lagunas, E. 1997. J. Physiol. 499:3-15; Gomez-Lagunas, E 2001. J. Gen. Physiol, 118:639-648), and that channel block by TEA, and scorpion toxins are two mutually exclusive events (Goldstein, S.A.N., and C. Miller. 1993. Biophys. J. 65:16131619). Therefore, we tested the ability of scorpion toxins to inhibit the collapse of G(k) in 0 K+. We have found that these toxins are not uniform regarding the capacity to protect G(k). Those toxins, whose binding to the channels is destabilized by external K+, are also effective inhibitors of the collapse of G(k), In addition to K+, other externally added cations also destabilize toxin block, with an effectiveness that. does not match the selectivity sequence of K+ channels. The inhibition of the drop of G(k) follows a saturation relationship with [toxin], which is fitted well by the Michaelis-Menten equation, with art apparent Kd bigger than that of block of the K+ current. However, another plausible model is also presented and compared with the Michaelis-Menten model. The observations suggest that those toxins that protect G(k) in 0 K+ do so by interacting either with the most external K+ binding site of the selectivity filter (Suggesting that the K+ occupancy of only that site of the pore may be enough to preserve G(k)) Or with sites capable of binding K+ located in the outer vestibule of the pore, above the selectivity filter.