G protein-gated inwardly rectifying potassium channel 1 F137S mutant (GIRK1 F137S)

The GIRK1 F137S mutant is a form of the G protein-gated inwardly rectifying potassium channel 1 (GIRK1, encoded by KCNJ3) in which phenylalanine at position 137 is replaced by serine. This single amino acid change converts GIRK1 from an inactive homomer to a channel that can form functional homomers with robust inward rectifying potassium currents and cooperate with other GIRK subunits for enhanced activity[1][2][4]. This mutation has been used in research and emerging therapies (notably experimental gene therapy for restoring photoreceptor activity in retinal degeneration) because it can restore or create membrane potassium currents in cells that have lost native electrical signaling, bypassing upstream signaling defects[6]. The channel maintains activation via G protein-coupled receptor pathways and also responds to exogenous channel modulators such as ML297[5]. While the wild-type GIRK1 requires heteromerization for activity, the F137S mutant displays unique properties, making it a valuable tool for dissecting channel function and developing novel therapies that require restoration of potassium conductance in excitable tissues[1][2][4][6].

Other names

GIRK1 F137S mutantKCNJ3 F137S mutantG protein-gated inwardly rectifying K+ channel 1 F137S mutant

Restores/increases channel activity by enabling the channel to conduct potassium currents as a mutant homomer and heteromer[1][2][3][4] Hyperpolarizes the membrane, reducing cell excitability[5] In gene therapy models, used to bypass defects in phototransduction signaling by re-establishing light-induced or GPCR-induced potassium flux in dormant cones[6]