Biology:KCNN2

Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2, also known as KCNN2, is a protein which in humans is encoded by the KCNN2 gene. KCNN2 is an ion channel protein also known as K_Ca2.2.

Function

Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The K_Ca2.2 protein is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. K_Ca2.2 is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. This protein is a member of the calcium-activated potassium channel family. Two transcript variants encoding different isoforms have been found for the KCNN2 gene.

In a 2009 study, SK2 (KCNN2) potassium channel was overexpressed in the basolateral amygdala using a herpes simplex viral system. This reduced anxiety and stress-induced corticosterone secretion at a systemic level. SK2 overexpression also reduced dendritic arborization of the amygdala neurons. In a 2015 study, it was found that UBE3A, the protein maternally deleted in Angelman syndrome, marks KCNN2 for degradation in the hippocampus, and that UBE3A deficiency is associated with an increase in KCNN2 levels. KCNN2 operates through a negative feedback loop to reduce glutamatergic NMDA receptor activation when it itself is activated by that same receptor. Angelman syndrome therefore leads to a reduction in glutamatergic NMDA receptor activation, which impairs long-term potentiation of hippocampal neurons and thus fear conditioning.

Target of acaricide

The corresponding K_Ca2 channel in the spider mite tetranychus urticae is the target of the acaricide acynonapyr in IRAC group 33.

See also

• SK channel
• Voltage-gated potassium channel

Further reading

• "International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels". Pharmacological Reviews 57 (4): 463–472. 2006. doi:10.1124/pr.57.4.9. PMID 16382103. 
• "SK2 encodes the apamin-sensitive Ca²⁺-activated K⁺ channels in the human leukemic T cell line, Jurkat". FEBS Letters 469 (2–3): 196–202. 2000. doi:10.1016/S0014-5793(00)01236-9. PMID 10713270. Bibcode: 2000FEBSL.469..196J. 
• "HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation". Proceedings of the National Academy of Sciences of the United States of America 97 (9): 4832–4837. 2000. doi:10.1073/pnas.090521697. PMID 10758170. Bibcode: 2000PNAS...97.4832L. 
• "Ca²⁺-activated K⁺ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization". Journal of Biological Chemistry 275 (51): 39954–39963. 2001. doi:10.1074/jbc.M001562200. PMID 10991935. 
• "Quantitative expression analysis of the small conductance calcium-activated potassium channels, SK1, SK2 and SK3, in human brain". Brain Research. Molecular Brain Research 85 (1–2): 218–220. 2001. doi:10.1016/S0169-328X(00)00255-2. PMID 11146124. 
• "Structure of the gating domain of a Ca²⁺-activated K⁺ channel complexed with Ca²⁺/calmodulin". Nature 410 (6832): 1120–1124. 2001. doi:10.1038/35074145. PMID 11323678. Bibcode: 2001Natur.410.1120S. 
• "Nuclear localization and dominant-negative suppression by a mutant SKCa3 N-terminal channel fragment identified in a patient with schizophrenia". Journal of Biological Chemistry 276 (30): 27753–27756. 2001. doi:10.1074/jbc.C100221200. PMID 11395478. 
• "Distribution of Ca²⁺-activated K channels, SK2 and SK3, in the normal and Hirschsprung's disease bowel". Journal of Pediatric Surgery 38 (6): 978–983. 2003. doi:10.1016/S0022-3468(03)00138-6. PMID 12778407. 
• "Molecular identification and functional roles of a Ca²⁺-activated K⁺ channel in human and mouse hearts". Journal of Biological Chemistry 278 (49): 49085–49094. 2004. doi:10.1074/jbc.M307508200. PMID 13679367. 
• "Calcium-dependent regulation of secretion in biliary epithelial cells: the role of apamin-sensitive SK channels". Gastroenterology 127 (3): 903–913. 2004. doi:10.1053/j.gastro.2004.06.047. PMID 15362045. 
• "Ca²⁺-activated K⁺ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-1α and the von Hippel-Lindau protein". The Journal of Physiology 571 (Pt 2): 349–359. 2006. doi:10.1113/jphysiol.2005.096818. PMID 16396931. 
• "Molecular coupling of a Ca²⁺-activated K⁺ channel to L-type Ca²⁺ channels via alpha-actinin2". Circulation Research 100 (1): 112–120. 2007. doi:10.1161/01.RES.0000253095.44186.72. PMID 17110593. 
• "Cell-cycle-dependent regulation of Ca²⁺-activated K⁺ channel in Jurkat T-lymphocyte". Journal of Pharmacological Sciences 104 (1): 94–98. 2007. doi:10.1254/jphs.SC0070032. PMID 17452806. 
• "KCa2 channels activation prevents [Ca²⁺i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia"]. Cell Death & Disease 2 (e147): e147. 2011. doi:10.1038/cddis.2011.30. PMID 21509037. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.