Wickman Kevin, Pu William T, Clapham David E
Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA.
Gene. 2002 Feb 6;284(1-2):241-50. doi: 10.1016/s0378-1119(01)00884-8.
Cardiac and neuronal G protein-gated potassium (K(G)) channels are activated by neurotransmitters such as acetylcholine, opioids, and dopamine. K(G) channel activation leads to an inhibition of synaptic transmission. K(G) 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 K(G) channels and their potential involvement in disease.
心脏和神经元G蛋白门控钾(K(G))通道可被乙酰胆碱、阿片类药物和多巴胺等神经递质激活。K(G)通道的激活会导致突触传递受到抑制。K(G)通道是由G蛋白门控内向整流钾(K(+))通道(GIRK)亚基组装形成的四聚体复合物。已鉴定出四种哺乳动物GIRK亚基(GIRK1 - 4)。在本研究中,我们确定了四个小鼠Girk基因的关键特征,包括序列、内含子/外显子结构、可变剪接事件以及候选转录起始点。小鼠Girk基因的组织方式相似,每个基因包含四到七个外显子。虽然小鼠Girk1和Girk2基因相对较大(>100 kb),但小鼠Girk3和Girk4基因较为紧凑(<20 kb)。通过可变剪接和/或使用不同的转录起始位点,鉴定出了Girk1、Girk3和Girk4的多种mRNA变体。这些发现应有助于未来旨在了解K(G)通道转录调控及其在疾病中潜在作用的研究。