KCNN2

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.{{cite journal | vauthors = Mitra R, Ferguson D, Sapolsky RM | title = SK2 potassium channel over-expression in basolateral amygdala reduces anxiety, stress-induced corticosterone and dendritic arborization | journal = Molecular Psychiatry | volume = 14 | issue = 9 | pages = 847–55, 827 | date = February 2009 | pmid = 19204724 | pmc = 2763614 | doi = 10.1038/mp.2009.9 }} 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.{{Cite journal | vauthors = Sun J, Zhu G, Liu Y, Standley S, Ji A, Tunuguntla R, Wang Y, Claus C, Luo Y, Baudry M, Bi X | title = UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis | journal = Cell Reports | volume = 12 | issue = 3 | pages = 449–461 | date = 2015-07-21 | pmid = 26166566 | pmc = 4520703 | doi = 10.1016/j.celrep.2015.06.023 | issn = 2211-1247 }}

The corresponding K_Ca2 channel in the spider mite tetranychus urticae is the target of the acaricide acynonapyr in IRAC group 33.{{Cite journal | vauthors = Hirata K, Kudo K, Amano T, Kawaguchi M | title = Effects of the novel acaricide acynonapyr on the calcium-activated potassium channel | journal = Pesticide Biochemistry and Physiology | volume = 204 | pages = 106074 | date = September 2024 | pmid = 39277387 | doi = 10.1016/j.pestbp.2024.106074 | doi-access = free }}

• SK channel
• Voltage-gated potassium channel

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• {{cite journal | vauthors = Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H | title = International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 463–472 | year = 2006 | pmid = 16382103 | doi = 10.1124/pr.57.4.9 | s2cid = 8290401 }}
• {{cite journal | vauthors = Jäger H, Adelman JP, Grissmer S | title = SK2 encodes the apamin-sensitive Ca²⁺-activated K⁺ channels in the human leukemic T cell line, Jurkat | journal = FEBS Letters | volume = 469 | issue = 2–3 | pages = 196–202 | year = 2000 | pmid = 10713270 | doi = 10.1016/S0014-5793(00)01236-9 | s2cid = 44455392 | doi-access = free | bibcode = 2000FEBSL.469..196J }}
• {{cite journal | vauthors = Liu QH, Williams DA, McManus C, Baribaud F, Doms RW, Schols D, Clercq E, Kotlikoff MI, Collman RG, Freedman BD | title = HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 9 | pages = 4832–4837 | year = 2000 | pmid = 10758170 | pmc = 18318 | doi = 10.1073/pnas.090521697 | bibcode = 2000PNAS...97.4832L | doi-access = free }}
• {{cite journal | vauthors = Desai R, Peretz A, Idelson H, Lazarovici P, Attali B | title = Ca²⁺-activated K⁺ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization | journal = Journal of Biological Chemistry | volume = 275 | issue = 51 | pages = 39954–39963 | year = 2001 | pmid = 10991935 | doi = 10.1074/jbc.M001562200 | doi-access = free }}
• {{cite journal | vauthors = Rimini R, Rimland JM, Terstappen GC | title = Quantitative expression analysis of the small conductance calcium-activated potassium channels, SK1, SK2 and SK3, in human brain | journal = Brain Research. Molecular Brain Research | volume = 85 | issue = 1–2 | pages = 218–220 | year = 2001 | pmid = 11146124 | doi = 10.1016/S0169-328X(00)00255-2 | doi-access = free }}
• {{cite journal | vauthors = Schumacher MA, Rivard AF, Bächinger HP, Adelman JP | title = Structure of the gating domain of a Ca²⁺-activated K⁺ channel complexed with Ca²⁺/calmodulin | journal = Nature | volume = 410 | issue = 6832 | pages = 1120–1124 | year = 2001 | pmid = 11323678 | doi = 10.1038/35074145 | bibcode = 2001Natur.410.1120S | s2cid = 205016620 }}
• {{cite journal | vauthors = Miller MJ, Rauer H, Tomita H, Rauer H, Gargus JJ, Gutman GA, Cahalan MD, Chandy KG | title = Nuclear localization and dominant-negative suppression by a mutant SKCa3 N-terminal channel fragment identified in a patient with schizophrenia | journal = Journal of Biological Chemistry | volume = 276 | issue = 30 | pages = 27753–27756 | year = 2001 | pmid = 11395478 | doi = 10.1074/jbc.C100221200 | doi-access = free }}
• {{cite journal | vauthors = Piotrowska AP, Solari V, Puri P | title = Distribution of Ca²⁺-activated K channels, SK2 and SK3, in the normal and Hirschsprung's disease bowel | journal = Journal of Pediatric Surgery | volume = 38 | issue = 6 | pages = 978–983 | year = 2003 | pmid = 12778407 | doi = 10.1016/S0022-3468(03)00138-6 }}
• {{cite journal | vauthors = Xu Y, Tuteja D, Zhang Z, Xu D, Zhang Y, Rodriguez J, Nie L, Tuxson HR, Young JN, Glatter KA, Vazquez AE, Yamoah EN, Chiamvimonvat N | title = Molecular identification and functional roles of a Ca²⁺-activated K⁺ channel in human and mouse hearts | journal = Journal of Biological Chemistry | volume = 278 | issue = 49 | pages = 49085–49094 | year = 2004 | pmid = 13679367 | doi = 10.1074/jbc.M307508200 | doi-access = free }}
• {{cite journal | vauthors = Feranchak AP, Doctor RB, Troetsch M, Brookman K, Johnson SM, Fitz JG | title = Calcium-dependent regulation of secretion in biliary epithelial cells: the role of apamin-sensitive SK channels | journal = Gastroenterology | volume = 127 | issue = 3 | pages = 903–913 | year = 2004 | pmid = 15362045 | doi = 10.1053/j.gastro.2004.06.047 }}
• {{cite journal | vauthors = Tajima N, Schonherr K, Niedling S, Kaatz M, Kanno H, Schonherr R, Heinemann SH | title = Ca²⁺-activated K⁺ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-1α and the von Hippel-Lindau protein | journal = The Journal of Physiology | volume = 571 | issue = Pt 2 | pages = 349–359 | year = 2006 | pmid = 16396931 | pmc = 1796787 | doi = 10.1113/jphysiol.2005.096818 }}
• {{cite journal | vauthors = Lu L, Zhang Q, Timofeyev V, Zhang Z, Young JN, Shin HS, Knowlton AA, Chiamvimonvat N | title = Molecular coupling of a Ca²⁺-activated K⁺ channel to L-type Ca²⁺ channels via alpha-actinin2 | journal = Circulation Research | volume = 100 | issue = 1 | pages = 112–120 | year = 2007 | pmid = 17110593 | doi = 10.1161/01.RES.0000253095.44186.72 | doi-access = free }}
• {{cite journal | vauthors = Morimoto T, Ohya S, Hayashi H, Onozaki K, Imaizumi Y | title = Cell-cycle-dependent regulation of Ca²⁺-activated K⁺ channel in Jurkat T-lymphocyte | journal = Journal of Pharmacological Sciences | volume = 104 | issue = 1 | pages = 94–98 | year = 2007 | pmid = 17452806 | doi = 10.1254/jphs.SC0070032 | doi-access = free }}
• {{cite journal | vauthors = Dolga AM, Terpolilli N, Kepura F, Nijholt IM, Knaus HG, D'Orsi B, Prehn JH, Eisel UL, Plant T, Plesnila N, Culmsee C | title = KCa2 channels activation prevents [Ca²⁺]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia | journal = Cell Death & Disease | volume = 2 | issue = e147 | pages = e147 | year = 2011 | pmid = 21509037 | pmc = 3122061 | doi = 10.1038/cddis.2011.30 }}

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{{PDB Gallery|geneid=3781}}

{{Ion channels|g3}}

Category:Ion channels

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