AN OPEN RECTIFIER POTASSIUM CHANNEL WITH 2-PORE DOMAINS IN TANDEM CLONED FROM RAT CEREBELLUM

Tandem pore domain K+ channels represent a new family of ion channels involved in the control of background membrane conductances. We report the structural and functional properties of a TWIK-related acid-sensi tive K+ channel (rTASK), a new member of this family cloned from rat c erebellum. The salient features of the primary amino acid sequence inc lude four putative transmembrane domains and, unlike other cloned tand em pore domain channels, a PDZ (postsynaptic density protein, disk-lar ge, zo-1) binding sequence at the C terminal. rTASK has distant overal l homology to a putative Caenorhabditis elegans K+ channel and to the mammalian clones TREK-1 and TWIK-1. rTASK expression is most abundant in rat heart, lung, and brain. When exogenously expressed in Xenopus o ocytes, rTASK currents activate instantaneously, are noninactivating, and are not gated by voltage. Because rTASK currents satisfy the Goldm an-Hodgkin-Katz current equation for an open channel, rTASK can be cla ssified an open rectifier. Activation of protein kinase A produces inh ibition of rTASK, whereas activation of protein kinase C has no effect . rTASK currents were inhibited by extracellular acidity. rTASK curren ts also were inhibited by Zn2+ (IC50 = 175 mu M), the local anesthetic bupivacaine (IC50 = 68 mu M), and the anti-convulsant phenytoin (simi lar to 50% inhibition at 200 mu M). By demonstrating open rectificatio n and open probability independent of voltage, we have established tha t rTASK is a baseline potassium channel.