Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2, also known asKCNN2, is aprotein which in humans is encoded by the KCNN2gene.[5] KCNN2 is anion channel protein also known as KCa2.2.[6][7]
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 KCa2.2 protein is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. KCa2.2 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 thecalcium-activated potassium channel family. Two transcript variants encoding different isoforms have been found for the KCNN2 gene.[6]
In a 2009 study, SK2 (KCNN2) potassium channel was overexpressed in the basolateralamygdala using a herpes simplex viral system. This reducedanxiety and stress-inducedcorticosterone secretion at a systemic level. SK2 overexpression also reduced dendritic arborization of the amygdala neurons.[8] In a 2015 study, it was found thatUBE3A, the protein maternally deleted inAngelman syndrome, marks KCNN2 for degradation in thehippocampus, and that UBE3A deficiency is associated with an increase in KCNN2 levels. KCNN2 operates through anegative feedback loop to reduceglutamatergicNMDA receptor activation when it itself is activated by that same receptor. Angelman syndrome therefore leads to a reduction in glutamatergic NMDA receptor activation, which impairslong-term potentiation of hippocampal neurons and thusfear conditioning.[9]
Piotrowska AP, Solari V, Puri P (2003). "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.doi:10.1016/S0022-3468(03)00138-6.PMID12778407.
Feranchak AP, Doctor RB, Troetsch M, Brookman K, Johnson SM, Fitz JG (2004). "Calcium-dependent regulation of secretion in biliary epithelial cells: the role of apamin-sensitive SK channels".Gastroenterology.127 (3):903–913.doi:10.1053/j.gastro.2004.06.047.PMID15362045.
