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), and that channel block by TEA(o) and scorpion toxins are two mutually exclusive events. 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.
Department Fisiologia, Edificio de Investigacion, 1er piso, Facultad de Medicina, University of México, Ciudad Universitaria, Apartado, Postal 70-250 México City D.F. 04510, México. froylan@ibt.unam.mx
Froylan
F
Gómez-Lagunas
Cesar V F
CV
Batista
Timoteo
T
Olamendi-Portugal
Martha E
ME
Ramírez-Domínguez
Lourival D
LD
Possani
D000595:Amino Acid Sequence; D000818:Animals; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D012604:Scorpion Venoms / Q000235:genetics / Q000494:pharmacology*; D012605:Scorpions; D051637:Shaker Superfamily of Potassium Channels
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D051637:Shaker Superfamily of Potassium Channels