KCNKO: Opening and closing the 2-P-domain potassium leak channel entails "C-type" gating of the outer pore

Essential to nerve and muscle function, little is known about how potassium leak channels operate. KCNKO opens and closes in a kinase-dependent fashio n. Here, the transition is shown to correspond to changes in the outer aspe ct of the ion conduction pore. Voltage-gated potassium (VGK) channels open and close via an internal gate; however, they also have an outer pore gate that produces "C-type" inactivation. While KCNKO does not inactivate, KCNKO and VGK channels respond in like manner to outer pore blockers, potassium, mutations, and chemical modifiers. Structural relatedness is confirmed: VG K residues that come close during C-type gating predict KCNKO sites that cr osslink (after mutation to cysteine) to yield channels controlled by reduct ion and oxidization. We conclude that similar outer pore gates mediate KCNK O opening and closing and VGK channel C-type inactivation despite their div ergent structures and physiological roles.