G-protein-activated inwardly rectifying potassium channel 1 (GIRK1 (also known as Kir3.1))

G-protein-activated inwardly rectifying potassium channel 1 (GIRK1, encoded by KCNJ3) is a subunit of the GIRK family of potassium channels that allows potassium ions to flow into, but less efficiently out of, excitable cells such as neurons and cardiac myocytes[1][3][5]. These tetrameric channels typically consist of GIRK1 in combination with other GIRK subunits (e.g., GIRK2, GIRK4), and are activated by the direct interaction of G protein βγ subunits, which are released upon activation of various GPCRs[1][3][5]. GIRK1-containing channels are key effectors in slowing heart rate in response to parasympathetic stimulation and in mediating inhibition in the central nervous system[2][4]. Activation hyperpolarizes the cell membrane, reduces excitability, and serves as a fundamental mechanism for physiological inhibition and rhythm modulation[1][3]. Dysregulation of GIRK1-associated channels contributes to several diseases, including cardiac arrhythmias and certain neuropsychiatric disorders, and selective activators and inhibitors are under investigation as therapeutic agents[3][5].

Other names

Kir3.1KCNJ3Girk1G protein-gated inward rectifier potassium channel 1G protein-coupled inwardly rectifying potassium channel 1

Drugs and neurotransmitters activate GIRK1-containing channels via G protein βγ subunits following GPCR activation, causing cell hyperpolarization - Direct binding and activation (for experimental small molecules such as ML297)