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Cloning and characterization of G protein-gated inward rectifier K+ channel (GIRK1) isoforms from heart and brain.

L Zhu, X Wu, M B Wu, K W Chan, D E Logothetis, W B Thornhill

J. Mol. Neurosci., 2001 Feb , 16, 21-32

A G protein-gated inward rectifier potassium (K+) channel (GIRK1a) has been cloned from different tissues (Kubo et al., 1993b; Dascal et al., 1993). Here we report the cloning of three additional novel isoforms of GIRK1a from rat atria and and one from human brain. These isoform cDNAs code for proteins that have identical N-termini, M1-H5-M2 (predicted transmembrane and pore domains), and post-M2 amino acid regions to GIRK1a (1-501 amino acids), but they have shorter C-termini (GIRK1b (1-309), GIRK1c (1-308), GIRK1d (1-235), and GIRK1e (1-253). These results indicated that isoforms were generated by alternative splicing and partial genomic analysis confirmed the presence of exons and introns in the rat GIRK1 gene. RNase protection analysis and immunoblot analysis indicated that the isoforms were expressed in both rat atria and brain but at lower levels versus GIRK1a. The physiological role that the isoforms may play in atrial and brain physiology remains to be determined.