CLONING OF A G-PROTEIN-ACTIVATED INWARDLY RECTIFYING POTASSIUM CHANNEL FROM HUMAN CEREBELLUM

Based on sequence homology with the rat atrial G protein-coupled musca rinic potassium channel (GIRK1 or KGA1/KGB1), a human cDNA encoding a G protein-activated inwardly rectifying K+ channel (HGIRK1) was isolat ed. The cDNA encodes a protein of 501 amino acids and shares 99% ident ity to rat GIRK1 in its total amino acid sequence. Southern blot analy sis of genomic DNA indicates a high degree of conservation among vario us species. In the human population a useful NlaIII restriction fragme nt length polymorphism was found in the coding sequence of HGIRK1. Go- expression of HGIRK1 and the 5-HT1A receptor in Xenopus oocytes result ed in opening of the channel upon treatment with serotonin. HGIRK1 cur rents showed strong inward rectification and could be blocked by extra cellular Ba2+. Northern blot analysis shows that HGIRK1 expression in human is most abundant in the brain, while lower levels are found in k idney and heart.