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KMID : 0578320030150010001
Molecules and Cells
2003 Volume.15 No. 1 p.1 ~ p.9
Molecular Mechanisms Mediating Inhibition of G Protein-coupled Inwardly-rectifying K+ Channels
Lei Q
Jones MB/Talley EM/Garrison JC/Bayliss DA
Abstract
Neuronal G protein-coupled inwardly-rectifying potassium channels (GIRKs, Kir3.x) can be activated or inhibited by distinct classes of receptors (Gai/o and Gaq/11-coupled, respectively), providing dynamic regulation of neuronal excitability. In this mini-review, we highlight findings from our laboratory in which we used a mammalian heterologous expression system to address mechanisms of GIRK channel regulation by Ga and Gbg subunits. We found that, like b1- and b2-containing Gbg dimers, GIRK channels are also activated by G protein bg dimers containing b3 and b4 subunits. By contrast, GIRK currents are inhibited by b5-containing Gbg dimers and/or by Ga proteins of the Gaq/11 family. The properties of Gb5-mediated inhibition suggest that b5-containing Gbg dimers act as competitive antagonists of other activating Gbg pairs on GIRK channels. Inhibition of GIRK channels by Ga subunits is specific to members of the Gaq/11 family and appears to result, at least in part, from activation of phospholipase C (PLC) and the resultant decrease in membrane levels of phosphatidylinositol-4,5-bisphosphate (PIP2), an endogenous co-factor necessary for GIRK channel activity; this Gaq/11 activated mechanism is largely responsible for receptor-mediated GIRK channel inhibition.
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