Abstract
The ability of voltage-gated potassium channel α-subunits to form heteromultimers has complicated efforts to use toxins to characterize potassium channels in native cells. Here I investigate the effects of subunit composition on toxin blocking affinity, using three members of the Shaker subfamily of potassium channel α-subunits (Kv1.1, Kv1.2 and Kv1.4), which are known to form heteromultimers in vivo,in the Xenopus oocyte expression system. These subunits were coexpressed as pairs in which one member was toxin-sensitive and the other relatively insensitive. The blocking affinity of two dendrotoxins (DTX-I and δ-DTX) and a scorpion toxin (tityustoxin-Kα) on the resulting mixed population of channels was measured to evaluate three models of toxin block. The single subunit model, in which a single toxin-sensitive subunit renders the channel toxin sensitive, best described all of the data for the two dendrotoxins and the block of tityustoxin-Kα for a mixed population of channels composed of Kv1.1 and Kv1.2 subunits. However, with tityustoxin-Kα, the data for a mixed population of Kv1.2 and Kv1.4 subunits was fit best by a model in which the toxin interacts with all four subunits for high-affinity block. The data suggest that subunit composition of potassium channels can have a large effect on toxin block and that different toxins yield strikingly diverse results with the same pair of subunits, even when they are nearly identical in blocking affinity for the toxin-sensitive subunit.
Footnotes
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- Abbreviations:
- α-DTX
- α-dendrotoxin
- CFS
- calcium-free solution
- δ-DTX
- δ-dendrotoxin
- DTX-I
- dendrotoxin-I
- FRS
- frog Ringer solution
- IC50
- compound concentration inhibiting 50% of potassium current
- ISS
- incubation saline solution
- tityustoxin-Kα
- scorpion toxin
- Received November 5, 1997.
- Accepted February 23, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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