CLONING AND LOCALIZATION OF A DOUBLE-PORE K-CHANNEL, KCNK1 - EXCLUSIVE EXPRESSION IN DISTAL NEPHRON SEGMENTS

The K-selective channel, TOK1, recently identified in yeast, displays the unusual structural feature of having two putative pore regions, in contrast to all previously cloned K channels. Using the TOK1 pore reg ions as probes, we identified a human kidney cDNA encoding a 337-amino acid protein (hKCNK1) with four transmembrane segments and two pore r egions containing the signature sequence of K channels. Amino acid ide ntity to TOK1 is only 15% overall but 40% at the pores. Northern analy sis indicates high expression of a 1.9-kb message in brain > kidney >> heart. Nephron segment localization, carried out in rabbit by reverse transcription-polymerase chain reaction, reveals that KCNK1 is expres sed in cortical thick ascending limb, connecting tubule, and cortical collecting duct. It was not detected in the proximal tubule, medullary thick ascending limb, distal convoluted tubule, and glomerulus. We co nclude that KCNK1 is a unique, double-pore, mammalian K channel, dista ntly related to the yeast channel TOK1, that is expressed in distal tu bule and is a candidate to participate in renal K homeostasis.