Genomic and functional characteristics of novel human pancreatic 2P domainK+ channels

We isolated three novel 2P domain K+ channel. subunits from human. The firs t two subunits, TALK-1 and TALK-2, are distantly related to TASK-2, Their g enes form a tight cluster of 25 kb on chromosome 6p21.1-p21.2, The correspo nding channels produce quasi-instantaneous and non-inactivating currents th at are activated at alkaline pHs, These currents are sensitive to Ba2+, qui nine, quinidine, chloroform, halothane, and isoflurane but are not affected by TEA, 4-AP, Cs+, arachidonic acid, hypertonic solutions, agents activati ng protein kinases C and A, changes of internal Ca2+ concentrations, and by activation of G(i) and G(q) proteins. TALK-1 is exclusively expressed in t he pancreas. TALK-2 is mainly expressed in the pancreas, but is also expres sed at a lower level in liver, placenta, heart, and lung. We also cloned a third subunit, named hTHIK-2 which is present in many tissues with high lev els again in the pancreas but which could not be functionally expressed. (C ) 2001 Academic Press.