Potassium sodium-activated channel subfamily T member 2 (KCNT2) (KCNT2)

Potassium sodium-activated channel subfamily T member 2 (KCNT2), commonly known as Slick (Sequence Like an Intermediate Conductance K+ channel), is a high-conductance potassium channel that is uniquely activated by intracellular sodium and chloride ions (UniProt Q6UVM3) [1]. It is widely expressed throughout the central nervous system and in the heart, where it plays a critical role in regulating membrane potential and neuronal firing patterns by contributing to the afterhyperpolarization phase following action potentials (IUPHAR/BPS) [2]. KCNT2 is closely related to the KCNT1 (Slack) channel, and the two can form heteromeric complexes that fine-tune potassium conductance in response to metabolic and ionic changes (PubMed: 14638918) [3]. Clinically, gain-of-function mutations in the KCNT2 gene have been identified as a cause of severe neurodevelopmental disorders, including West syndrome and early infantile epileptic encephalopathy type 57 (PubMed: 29604961) [5]. Because these mutations lead to increased potassium conductance and paradoxical neuronal hyperexcitability, KCNT2 is an emerging therapeutic target; the anti-arrhythmic drug quinidine is often explored as an off-label treatment to inhibit the overactive channel and reduce seizure frequency (PubMed: 30104458) [6]. However, achieving high selectivity for KCNT2 over other potassium channels remains a significant challenge in drug development, particularly regarding potential cardiac safety concerns.

Other names

SlickKCa4.2SLO2.1Sequence like an intermediate conductance K+ channelPotassium channel subfamily T member 2

Modulation of potassium conductance in response to intracellular sodium and chloride levels; therapeutic focus is primarily on channel inhibition to counteract gain-of-function mutations in epilepsy (PubMed: 30104458) [6].