KCNJ3

KCNJ3 is a gene that encodes the G-protein-activated inwardly rectifying potassium channel 1 (GIRK-1), also known as Kir3.1. It is a member of the Kir family of inward-rectifier potassium channels and contributes to tightly controlled resting membrane potential and excitability in neurons and cardiac cells.

GIRK-1 subunits form tetrameric channels that can assemble as homotetramers or as heterotetramers with other Kir3 subunits, such as GIRK2 (Kir3.2) or GIRK4 (Kir3.4). These channels participate in signaling pathways linked to Gi/o-coupled receptors and contribute to the native IKACh-type currents that regulate cellular excitability in the heart and brain. In the heart, GIRK1-containing channels contribute to acetylcholine- and adenosine-mediated responses that slow heart rate; in the brain, they shape neuronal signaling and synaptic integration.

Expression of KCNJ3 is reported in various tissues, with notable presence in atrial tissue and several brain regions. The channel’s activity is controlled by the release of Gβγ subunits from Gi/o-proteins following receptor activation, leading to increased potassium conductance, hyperpolarization, and reduced cellular excitability. Pharmacological study of GIRK channels has used specific blockers and modulators to dissect subunit composition and function; tertiapin is among the agents used to inhibit GIRK channels in experimental settings.

Clinical and research interest around KCNJ3 centers on how variations in GIRK1 influence cardiac rhythm and neural signaling. Genetic variants have been investigated for associations with cardiac conduction and other disorders, though the clinical significance remains an area of ongoing study. Kir3.1-containing channels continue to be a focus for understanding Gi/o-mediated signaling in heart and brain.