Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

Abstract

The sodium‐activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high‐conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093–2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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.…”

“…Variants of KCNT2 (SLICK, “sequence like an intermediate conductance K + “, Slo2.1) have not previously been linked to a human phenotype despite ~74% gene sequence homology and postulated hetero-tetramerization between the two subunits in at least some brain regions (Lim et al, 2014, Chen et al, 2009, Bhattacharjee et al, 2003, Lim et al, 2016). Slick is set apart by its rapid activation kinetics, sensitivity to intracellular chloride and cell volume variations, slight sodium permeability as well as selective localization in brain regions such as the sub-plate of the cerebral cortex in utero and the hippocampus and cortex in the adult, suggesting that the channel plays an ongoing role in cerebral function (Oeschger et al, 2012, Bhattacharjee et al, 2003, Tejada et al, 2014, Rizzi et al, 2016, Bhattacharjee et al, 2002). …”

KCNT1mutations in seizure disorders: the phenotypic spectrum and functional effects

“…This may be because the expression patterns of the two genes do not completely overlap, suggesting some differences in their function. Differences in expression patterns of the two genes have been described in rodents 68 69. Data from the Allen Brain Atlas (http://human.brain-map.org) indicate that differing expression patterns of the two genes also occur in humans.…”

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

“…Studies of its regional distribution, however, indicate that this is unlikely to be a major role for K Na 1.1 subunits. Unlike the ubiquitous K Ca 1.1, K Na 1.1 is primarily expressed in central and peripheral neurons, with little expression in other tissues except for the testes and kidney (Joiner et al, 1998;Bhattacharjee et al, 2002;Paulais et al, 2006;Brown et al, 2008;Nuwer et al, 2010;Rizzi et al, 2016).…”