Sodium-activated potassium channel subfamily T member 2 (KCNT2)

Sodium-activated potassium channel subfamily T member 2 (KCNT2), also known as Slick, is a transmembrane protein that forms a potassium-selective pore activated by intracellular sodium and chloride ions (UniProt Q6UVM3). It is primarily expressed in the central nervous system, where it regulates neuronal excitability and the timing of action potential firing by contributing to the late phase of afterhyperpolarization (PubMed: 14645203). KCNT2 is a significant therapeutic target because gain-of-function mutations in the encoding gene are associated with severe neurological conditions, including early infantile epileptic encephalopathy and developmental delay (PubMed: 30104304). These mutations cause the channel to remain open more frequently, leading to paradoxical neuronal hyperexcitability. Pharmacological intervention typically focuses on channel inhibitors, such as the anti-arrhythmic drug quinidine, which has been used off-label to reduce seizure frequency in patients with KCNT2-related epilepsy (PubMed: 31433878). However, the lack of highly selective KCNT2 inhibitors remains a challenge, as current drugs often interact with other ion channels, leading to potential cardiac and systemic side effects. Understanding the structure and gating of KCNT2 is essential for developing targeted therapies that can mitigate the neurological symptoms associated with its dysfunction.

Other names

SlickKCa4.2SLO2.1Potassium channel subfamily T member 2Sequence like calcium-activated K+ channel

Channel inhibition to reduce potassium conductance in gain-of-function variants