What is SK3

SK3 is a small-conductance calcium-activated potassium channel partly responsible for the calcium-dependent after hyperpolarisation current (IAHP). It belongs to a family of channels known as small-conductance potassium channels, which consists of three members – SK1, SK2 and SK3 (KCNN1, 2 and 3 respectively), which share a 60-70% sequence identity.[1] These channels have acquired a number of alternative names, however a NC-IUPHAR has recently achieved consensus on the best names, KCa2.1 (SK1), KCa2.2 (SK2) and KCa2.3 (SK3).[2] Small conductance channels are responsible for the medium and possibly the slow components of the IAHP.

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Classification of SK channel

The SK channel family contains 4 members - SK1, SK2, SK3, and SK4.

Pathology of SK3

Mutations in KCa2.3 are suspected to be a possible underlying cause for several neurological disorders, including schizophrenia, bipolar disorder, Alzheimer’s disease, anorexia nervosa and ataxia[6][7][8] as well as myotonic muscular dystrophy.

Structure of SK3

KCa2.3 contains 6 transmembrane domains, a pore-forming region, and intracellular N- and C- termini[3][1] and is readily blocked by apamin. The gene for KCa2.3, KCNN3, is located on chromosome 1q21.

Blockers of SK channel

All SK channels can be pharmacologically blocked by quaternary ammonium salts of a plant-derived neurotoxin bicuculline.[6] In addition, SK channels(SK1-SK3) are sensitive to blockade by the bee venom apamin, [7] but SK4 (IK) is not. and the scorpion venom tamapin.[8]

Physiology of SK3

KCa2.3 channels play a major role in human physiology, particularly in smooth muscle relaxation. The expression level of KCa2.3 channels in the endothelium influences arterial tone by setting arterial smooth muscle membrane potential. The sustained activity of KCa2.3 channels induces a sustained hyperpolarisation of the endothelial cell membrane potential, which is then carried to nearby smooth muscle through gap junctions.[5] Blocking the KCa2.3 channel or suppressing KCa2.3 expression causes a greatly increased tone in resistance arteries, producing an increase in peripheral resistance and blood pressure.

Expression of SK3

KCa2.3 is found in almost every tissue in the human body, with exceptions being the pancreas, placenta, adipose tissue, liver, prostate and skin.[1] KCa2.3 is most abundant in regions of the brain, but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in smooth muscle, including the rectum, corpus cavernosum, colon, small intestine and myometirum.[1] The expression level of KCNN3 is dependent on hormonal regulation, particularly by the sex hormone estrogen. Estrogen not only enhances transcription of the KCNN3 gene, but also affects the activity of KCa2.3 channels on the cell membrane.

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