Inward rectifier potassium channel 18 (Kir2.6) (Kir2.6)

Inward rectifier potassium channel 18 (Kir2.6) is a protein encoded by the KCNJ18 gene that functions as an inwardly rectifying potassium channel specifically in skeletal muscle [1, 2]. It plays a vital role in stabilizing the resting membrane potential and ensuring proper muscle excitability by allowing potassium efflux during the late stages of the action potential [3, 9]. The expression of Kir2.6 is uniquely regulated by thyroid hormone through a thyroid hormone response element in its promoter, making it highly sensitive to thyroid status [1, 7]. Mutations in the KCNJ18 gene are a major cause of thyrotoxic hypokalemic periodic paralysis (TPP), a condition characterized by sudden episodes of muscle weakness and low serum potassium in hyperthyroid patients [1, 6]. These mutations typically result in a loss of channel function or dominant-negative effects on other Kir2 channels, leading to membrane depolarization and muscle inexcitability [3, 9]. While no drugs currently target Kir2.6 specifically for clinical use, small molecule inhibitors like ML133 have been developed as research tools to study the Kir2 family [12, 14]. Understanding Kir2.6 function is essential for diagnosing susceptibility to periodic paralysis and developing potential treatments for muscle channelopathies [4, 13].

Other names

KCNJ18Inwardly rectifying potassium channel 18TTPP2Inward rectifier K(+) channel Kir2.6

Inhibition of the Kir2 family of inward rectifier potassium channels