MOLECULAR-CLONING, FUNCTIONAL EXPRESSION AND LOCALIZATION OF AN INWARD RECTIFIER POTASSIUM CHANNEL IN THE MOUSE-BRAIN

We have cloned an inward-rectifier potassium channel from a mouse brai n cDNA library, studied its distribution in the brain by in situ hybri dization and determined the chromosomal localization of the gene. A mo use brain cDNA library was screened using a fragment of the mouse macr ophage IRK1 cDNA as a probe. Two duplicate clones of similar to 5.5 kb were obtained. Xenopus ococytes injected with cRNA derived from the c lone expressed a potassium channel with inwardly rectifying channel ch aracteristics. The amino acid sequence of the clone was identical to t hat of IRK1 recently cloned from a mouse macrophage cell line. In situ hybridization study showed the mouse brain IRK1 to be generally distr ibuted throughout the brain, but in particular subsets of neurons at h igh levels. The gene was placed in the distal region of mouse chromoso me 11, which contains several uncloned neurological mutations. These r esults provide the first demonstration of the cloning and distribution of an inward rectifier potassium channel from the nervous system.