Transcriptional Regulation of the Sodium-activated Potassium Channel SLICK (KCNT2) Promoter by Nuclear Factor-κB

Abstract

Background:The active role of SLICK channels and their regulation in neurons are largely unknown. Results: SLICK transcription is highly dependent upon NFB activation in peripheral and central neurons. Conclusion: SLICK is an evolutionarily conserved NFB-regulated gene. Significance: SLICK channels may confer neuroprotection during ischemic conditions.

<p>Long Non-Coding RNA HAND2-AS1 Inhibits Growth and Migration of Gastric Cancer Cells Through Regulating the miR-590-3p/KCNT2 Axis</p>

“…KCNT2 was revealed to contain binding sites for Nuclear Factor-κB. 20 Yang et al 21 recently performed a bioinformatic-based study and revealed low KCNT2 level was associated with the worse survival of patients with melanoma. 21 We demonstrated that KCNT2 had decreased expression in tumor tissues and cell lines, and was a target of miR-590-3p.…”

A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters Ion Selectivity and Causes Epileptic Encephalopathy

“…Despite high sequence homology and structural similarities, KCNT1 and KCNT2 channels appear to have very different roles in physiological as well as pathophysiological conditions, likely resulting from distinct, often non-overlapping, patterns of localization within the central and peripheral nervous system (Bhattacharjee et al, 2002, Bhattacharjee et al, 2003, Rizzi et al, 2016, Tomasello et al, 2015). Thus, it follows that while gain-of-function KCNT1 epilepsy mutations reported thus far are proposed to selectively enhance K + currents resulting in inhibitory neuronal suppression (Barcia et al, 2012, Kim and Kaczmarek, 2014), the Phe240Leu KCNT2 mutation suggests a uniquely contrasting mechanism wherein increased inward I Na may affect the precisely synchronized Na + and K + exchange that is crucial to normal intrinsic neuronal excitability.…”

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels

“…Nevertheless, several observations suggest that it serves a protective function during ischemia or tissue injury, the function proposed by the very first publication describing Na + -activated K + currents (Kameyama et al, 1984). In neurons, the promoter for the gene is regulated by nuclear factor-kB, which is activated under conditions of hypoxia or injury (Tomasello et al, 2015). In the nematode Caenorhabditis elegans, deletion of the gene for SLO-2, the ortholog to mammalian K Na channels, alters the sensitivity of the animals to hypoxia, although reports differ in the direction of the change in sensitivity (Yuan et al, 2003;Zhang et al, 2013b).…”