Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion.
Genomic microarray analysis of genes specifically expressed in a pure cell isolate from a heterocellular organ identified the likely K efflux channel associated with the gastric H-K-ATPase. The function of this channel is to supply K to the luminal surface of the pump to allow H for K exchange. KCNQ1-KCNE2 was the most highly expressed and significantly enriched member of the large variety of K channels expressed in the gastric epithelium. The function of this K channel in acid secretion was then shown by inhibition of secretion in isolated gastric glands with specific KCNQ inhibitors and by colocalization of the channel with the H-K-ATPase in the secretory canaliculus of the parietal cell. KCNQ1-KCNE2 appears to be the K efflux channel that is essential for gastric acid secretion.
Lambrecht
Nils W G
NW
Department of Pathology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. nilslam@ucla.edu
Yakubov
Iskandar
I
Scott
David
D
Sachs
George
G
D000165:Acridine Orange / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000632:Aminopyrine / Q000737:chemistry; D000818:Animals; D002469:Cell Separation; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism*; D005434:Flow Cytometry; D005744:Gastric Acid / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism*; D007150:Immunohistochemistry; D051657:KCNQ1 Potassium Channel / Q000096:biosynthesis*; D008297:Male; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry*; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis* / Q000737:chemistry; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C489619:KCNE2 protein, human; D051657:KCNQ1 Potassium Channel; D009841:Oligonucleotides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018075:RNA, Complementary; D012333:RNA, Messenger; D000632:Aminopyrine; D000251:Adenosine Triphosphatases; D000165:Acridine Orange; D011188:Potassium