Inward rectifier potassium channel 2.2 (Kir2.2)

Inward rectifier potassium channel 2.2 (Kir2.2), encoded by the KCNJ12 gene, is a key member of the inwardly rectifying potassium (Kir) channel family (UniProt Q14500) [2]. These channels are characterized by their ability to conduct potassium ions more readily into the cell than out of it, a property known as inward rectification (Wikipedia) [16]. This rectification is primarily achieved through the voltage-dependent blockade of the channel pore by intracellular polyamines and magnesium ions at depolarized potentials (PMC) [4, 16]. Kir2.2 is widely expressed in the heart, brain, and skeletal muscle, where it plays a critical role in stabilizing the resting membrane potential and shaping the late phase of the action potential (Creative Biolabs) [1]. In the heart, it contributes to the IK1 current, which is essential for maintaining cardiac rhythm and excitability (GeneCards) [6]. Mutations in KCNJ12 have been linked to various pathologies, including familial dilated cardiomyopathy and certain types of cancer like esophageal squamous cell carcinoma (PubMed) [1, 21]. While specific drugs targeting Kir2.2 are still in development, small molecules like ML133 have been identified as inhibitors of the Kir2 family, and the channel's modulation remains a significant area of interest for treating cardiac arrhythmias and other excitability-related disorders (PMC) [12, 15].

Other names

KCNJ12IRK2IRK-2KCNJN1Potassium inwardly-rectifying channel subfamily J member 12ATP-sensitive inward rectifier potassium channel 12hIRK1Kir2.2v

Inhibition of the channel pore to reduce potassium conductance; activation of the channel to increase resting membrane stability; relief of polyamine-mediated block to enhance outward current.