• Joseph F Cotten, Hilary Liao Zou, Canhui Liu, John D Au, and C Spencer Yost.
• Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Ave., Room S-261, Box 0542, San Francisco, CA 94143, USA.
• Brain Res. Mol. Brain Res. 2004 Sep 28; 128 (2): 112-20.

AbstractThe TWIK-related, Acid Sensing K (TASK-2; KCNK5) potassium channel is a member of the tandem pore (2P) family of potassium channels and mediates an alkaline pH-activated, acid pH-inhibited, outward-rectified potassium conductance. In previous work, we demonstrated TASK-2 protein expression in newborn rat cerebellar granule neurons (CGNs). In this study, we demonstrate TASK-2 functional expression in CGNs as a component of the pH-sensitive, volatile anesthetic-potentiated, standing-outward potassium conductance (I(K,SO)). Using excised, inside-out patch-clamp technique, we studied CGNs grown in primary culture. We identified four distinct, noninactivating single channel potassium conductances, Types 1-4. Types 1-3 have previously been attributed to TASK-1 (KCNK3), TASK-3 (KCNK9) and TASK-1/TASK-3 heteromers, and TREK-2 (KCNK10) 2P potassium channel function, respectively; however, the Type 4 conductance is currently unassigned. Previous studies demonstrated that Type 4 single channel activity is potentiated by extracellular, alkaline pH and cytoplasmic arachidonic acid (10-20 microM) and inhibited by cytoplasmic tetraethylammonium (TEA; 1 mM). We determined that heterologously expressed TASK-2 channels have single channel gating, conductance properties and pH sensitivity identical to the Type 4 conductance. Additionally, we found that TASK-2 single channel activity, like the Type 4 conductance is potentiated by cytoplasmic arachidonic acid (20 microM) and inhibited by cytoplasmic TEA (1 mM). We conclude that TASK-2 mediates the Type 4 single channel conductance in CGNs as a component of I(K,SO).

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