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 (Gómez-Lagunas, F. 1997. J. Physiol. 499:3–15; Gómez-Lagunas, F. 2001. J. Gen. Physiol. 118:639–648), and that channel block by TEA_o and scorpion toxins are two mutually exclusive events (Goldstein, S.A.N., and C. Miller. 1993. Biophys. J. 65:1613–1619). 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 an 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.