Slick (Slo2.1), a Rapidly-Gating Sodium-Activated Potassium Channel Inhibited by ATP

Neuronal stressors such as hypoxia and firing of action potentials at very high frequencies cause intracellular Na⁺ to rise and ATP to be consumed faster than it can be regenerated. We report the cloning of a gene encoding a K⁺ channel, Slick, and demonstrate that functionally it is a hybrid between two classes of K⁺ channels, Na ⁺-activated (K_Na) and ATP-sensitive (K_ATP) K⁺ channels. The Slick channel is activated by intracellular Na ⁺ and Cl^- and is inhibited by intracellular ATP. Slick is widely expressed in the CNS and is detected in heart. We identify a consensus ATP binding site near the C terminus of the channel that is required for ATP and its nonhydrolyzable analogs to reduce open probability. The convergence of Na⁺, Cl^-, and ATP sensitivity in one channel may endow Slick with the ability to integrate multiple indicators of the metabolic state of a cell and to adjust electrical activity appropriately.