G protein-gated inwardly rectifying potassium (GIRK or Kir3) channels constitute
one subfamily of potassium-selective ion channels that regulate neuronal activity
and heart rate. GIRK channels have been implicated in many biological
processes, including pain perception, learning and memory, food intake, and
reward. Structurally, GIRK channels consist of 4 subunits, able to form
homotetramers or heterotetramers within the cell membrane. Activation of these
channels occurs through a signal transduction cascade originating from ligandstimulated
G-protein coupled receptors (GPCRs). This results in hyperpolarization
of the cell membrane. With the variety of biological processes GIRK channels are
involved in, understanding the interaction of the GPCR signaling cascade with
GIRK channels could provide a beneficial therapeutic target.
Using a variety of molecular biology techniques, I synthesized various chimeric
proteins to investigate the GIRK channel and GPCR relationship, specifically
focusing on amino acid residues promoting the coupling of GIRK1 with the GABAB
receptor. Functional and biochemical assays in native systems suggest the Cterminal
region and pore residue of the GIRK1 subunit are necessary to mediate a
large receptor-induced response from the GIRK channel. Investigating this
phenomenon further can determine how the identified GIRK1 channel domains
are mediating efficient GABAB receptor coupling.
Additional contributors: Nicole Wydeven; Kevin Wickman (faculty mentor)
This research was supported by NIH grants RO1 MH061933, P50 DA011806, and R21029343 DA.
The Identification of Girk Channel Domains that Facilitate Rapid and Efficient Coupling to G Protein- Coupled Receptors.
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