Repulsion between tetraethylammonium ions in cloned voltage-gated potassium channels

Teraethylammonium ion (TEA⁺)blocks voltage-gated K⁺ channels by acting at two sites located at opposite ends of the aqueous pore. This allowed us to test two predictions made by models of ion permeation, namely that K⁺ channels can be simultaneously occupied by multiple ions and that the ions repel each other. We show that externally applied TEA⁺ antagonize block by internal TEA⁺ and vice versa. The antagonism is less than predicted for competitive binding, hence TEA⁺ may occupy both sites simultaneously. External TEA⁺ and internal TEA⁺ reduce each others affinity 4-to 5-fold. In addition, K⁺ antagonizes block by TEA⁺ at the opposite side of the membrane, and external TEA⁺ antagonizes is block by internal Ba²⁺. The antagonism between ions applied at opposite sides of the membrane may be common to all cations binding to K⁺ channels.