Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain

Abstract

SK2 (KCa2.2) channels are voltage-independent Ca2+-activated K+ channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex. In hippocampus, SK2-like immunoreactivity could be detected in strata oriens and radiatum of area CA1-CA2 and in the molecular layer. In the amygdala, SK2-like immunoreactivity was highest in the basolateral nuclei, while in neocortex, staining was mainly found enriched in layer V. Activation of SK2 channels is thought to regulate neuronal excitability in brain by contributing to the medium afterhyperpolarization. However, SK2 channels are blocked by apamin with a sensitivity that suggests heteromeric channels. The herein first shown expression of SK2 human isoform b in brain could explain the variability of electrophysiological findings observed with SK2 channels.

KCNN2 mutation in autosomal‐dominant tremulous myoclonus‐dystonia

“…In humans, it is strongly expressed in the liver and brain (particular the cerebellum, caudate nucleus and hippocampus) [19]. There are four different SK2 channel isoforms (SK2‐std, SK2‐long, SK2‐ssv and SK2‐hib) in the human brain [20] with important roles in the regulation of neuronal excitability and modulation of spike‐firing frequency and calcium transients in dendritic spines [21].…”

Small and Intermediate Calcium Activated Potassium Channels in the Heart: Role and Strategies in the Treatment of Cardiovascular Diseases

“…KCNN2 is located on chromosome 5 and encodes the SK2 (KCa2.2) channel. Two human isoforms of variable sizes have been currently reported (Willis et al, 2017). The shortest spliced variant, SK2 isoform b (SK2-hib), lacks the N-terminal region and the S1-S5 transmembrane domains (Willis et al, 2017).…”

“…Two human isoforms of variable sizes have been currently reported (Willis et al, 2017). The shortest spliced variant, SK2 isoform b (SK2-hib), lacks the N-terminal region and the S1-S5 transmembrane domains (Willis et al, 2017). Thus, these channels exhibit the strongest affinity for apamin (IC 50 30-200 pM) or tamapin (Wulff et al, 2007).…”

Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress

“…These channels regulate delayed rectifier currents during the action potential [ 73 ]. In addition, the expression of Kcnn1 and Kcnn2 transcripts, which encode the calcium-activated potassium channel subfamily N members KCa2.1 and KCa2.2 [ 74 ], respectively, were both increased 24 h following a 5th restraint in the female pPVT. These channels augment the afterhyperpolarization phase of the action potential and thereby have inhibitory effects in the neurons they are expressed in [ 75 ].…”