Inhibition of the Collapse of the Shaker K+ Conductance by Specific Scorpion Toxins

The Shaker B K+ conductance (GK) collapses when the channels are closed (deactivated) in Na+ solutions that lack K+ ions. Also, it is known that external TEA (TEAo) impedes the collapse of GK (Gómez-Lagunas, F. 1997. J. Physiol. 499:3–15; Gómez-Lagunas, F. 2001. J. Gen. Physiol. 118:639–648), and that channel block by TEAo 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 GK in 0 K+. We have found that these toxins are not uniform regarding the capacity to protect GK. Those toxins, whose binding to the channels is destabilized by external K+, are also effective inhibitors of the collapse of GK. 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 GK 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 GK 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 GK) or with sites capable of binding K+ located in the outer vestibule of the pore, above the selectivity filter.

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