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Am J Physiol Cell Physiol 279: C771-C784, 2000;
0363-6143/00 $5.00
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Vol. 279, Issue 3, C771-C784, September 2000

Cloning and functional expression of human retinal Kir2.4, a pH-sensitive inwardly rectifying K+ channel

Bret A. Hughes1,2, Gyanendra Kumar1, Yukun Yuan1, Anuradha Swaminathan1, Denise Yan1, Ashish Sharma1, Lisa Plumley4, Teresa L. Yang-Feng4, and Anand Swaroop1,3

Departments of 1 Ophthalmology and Visual Sciences, 2 Physiology, and 3 Human Genetics, University of Michigan, Ann Arbor, Michigan 48105; and 4 Department of Genetics, Yale University, New Haven, Connecticut 06520

To identify novel potassium channel genes expressed in the retina, we screened a human retina cDNA library with an EST sequence showing partial homology to inwardly rectifying potassium (Kir) channel genes. The isolated cDNA yielded a 2,961-base pair sequence with the predicted open reading frame showing strong homology to the rat Kir2.4 (rKir2.4). Northern analysis of mRNA from human and bovine tissues showed preferential expression of Kir2.4 in the neural retina. In situ hybridization to sections of monkey retina detected Kir2.4 transcript in most retinal neurons. Somatic hybridization analysis and dual-color in situ hybridization to metaphase chromosomes mapped Kir2.4 to human chromosome 19 q13.1-q13.3. Expression of human Kir2.4 cRNA in Xenopus oocytes generated strong, inwardly rectifying K+ currents that were enhanced by extracellular alkalinization. We conclude that human Kir2.4 encodes an inwardly rectifying K+ channel that is preferentially expressed in the neural retina and that is sensitive to physiological changes in extracellular pH.

potassium channels; nucleotide sequence; chromosomal localization


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