A G-PROTEIN-ACTIVATED INWARDLY RECTIFYING K+ CHANNEL (GIRK4) FROM HUMAN HIPPOCAMPUS ASSOCIATES WITH OTHER GIRK CHANNELS

Transcripts of a gene, GIRK4, that encodes for a 419-amino-acid protei n and shows high structural similarity to other subfamily members of G -protein-activated inwardly rectifying K+ channels (GIRK) have been id entified in the human hippocampus. When expressed in Xenopus oocytes, GIRK4 yielded functional GIRK channels with activity that was enhanced by the stimulation of coexpressed serotonin 1A receptors. GIRK4 poten tiated basal and agonist-induced currents mediated by other GIRK chann els, possibly because of channel heteromerization. Despite the structu ral similarity to a putative rat K-ATP channel, no ATP sensitivity or K-ATP-typical pharmacology was observed for GIRK4 alone or GIRK4 trans fected in conjunction with other GIRK channels in COS-7 cells. In rat brain, GIRK4 is expressed together with three other subfamily members, GIRK1-3, most likely in identical hippocampal neurons. Thus, heterome rization or an unknown molecular interaction may cause the physiologic al diversity observed within this class of K+ channels.