Structural characterization of the mouse Girk genes

Abstract

Cardiac and neuronal G protein-gated potassium (KG) channels are activated by neurotransmitters such as acetylcholine, opioids, and dopamine. KG channel activation leads to an inhibition of synaptic transmission. KG channels are tetrameric complexes formed by assembly of G protein-gated, inwardly-rectifying potassium (K+) channel (GIRK) subunits. Four mammalian GIRK subunits (GIRK1–4) have been identified. In this study, we identify key features of the four mouse Girk genes including sequence, intron/exon structures, alternative splicing events, and candidate transcriptional start points. The mouse Girk genes are organized similarly, each containing four to seven exons. While the mouse Girk1 and Girk2 genes are relatively large (>100 kb), mouse Girk3 and Girk4 genes are compact (<20 kb). Multiple mRNA variants of Girk1, Girk3, and Girk4 were identified, existing by virtue of alternative splicing and/or usage of distinct transcription initiation sites. These findings should facilitate future studies aimed at understanding the transcriptional regulation of KG channels and their potential involvement in disease.