TASK-3
TASK-3 (KCNK9 or K2P9.1) is a member of the family of leak or two-pore-domiain potassium channels, which have 4 transmembrane segments and 2 P-domains, and is one of the major determinants of cell membrane potential and input resistance[1]. TASK-3 (TWIK-related acid-sensitive K+ channel) is involved in cortical function and might also be involved in the formation of cortical neural circuits. The ion channel is >50% identical to TASK-1 at the amino acid level, and in whole-cell recordings the two channels have similar physiological properties but different pH sensitivities. TASK-1 and TASK-3 are co-expressed in a number of different cell types, suggesting the possibility that they form heterodimeric channels[2]. TASK-3 is particularly abundant in the hippocampus, cerebellum and cortex, and in specific nuclei including the locus coeruleus, paraventricular nuclei of thalamus and the dorsal raphe. Its activity has been shown to regulate both neurotransmitter release as well as mediating the effects of neurotransmitter activation including the activity of 5-HT-releasing neurons of the dorsal raphe. TASK-3 inhibitors could lead to therapeutic agents against neurological conditions including sleep disorders, neurodegeneration, cognitive impairment, Parkinson′s disease, Huntington’s disease, or major depressive disorder[3].
[1] Y. Bando et al. Dysfunction of KCNK potassium channels impairs neuronal migration in the developing mouse cerebral cortex. Cereb Cortex. 2014 Apr;24(4):1017-29.
[2] E.M. Talley et al. Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action. J Biol Chem. 2002 May 17;277(20):17733-42.
[3] C.A. Coburn et al. Discovery of a pharmacologically active antagonist of the two-pore-domain potassium channel K2P9.1 (TASK-3). ChemMedChem. 2012 Jan 2;7(1):123-33.