KCa3.1 | IK | SK4 | Intermediate Conductance Calcium-activated Potassium Channel Protein 4
Family:
Calcium- and sodium-activated Potassium channels
Members:
Today, eight human calcium-activated channels are known: KCa1.1 (also known as BK or Maxi-K), KCa2.1 (also known as SK1), KCa2.2 (also known as SK2), KCa2.3 (also known as SK3) , KCa3.1 (also known as IK or SK4), KCa4.1, KCa4.2, KCa5.1
Topology:
KCa channels are made up of two different subunits, alpha and beta. The alpha subunit contains six or seven trans-membrane regions and forms homo- or heter-tetramers. The beta subunit has a regulative function and contains 2 trans-membrane regions.
Regulation:
This family of ion channels is, for the most part, activated by intracellular Ca2+. However, some of these channels (the KCa4 and KCa5 channels) are responsive instead to other intracellular ligands, such as Na+, Cl−, and pH. Furthermore, multiple members of family are both ligand and voltage activated.
KCa3.1 Background Information
KCa3.1 (aka SK4 or Gardos channel) is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. KCa3.1 is involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation. In addition to functions in cell cycle progression and cellular proliferation, KCa3.1 channels play an important immunoregulatory role, including participation in pathologic mechanisms that are associated with the inflammatory and proliferative cascades that characterise autoimmune diseases such as rheumatoid arthritis. KCa3.1 is involved in lymphocyte activation, and in the proliferation and migration of T cells, B cells, mast cells, macrophages and fibroblasts.
Gene:
KCNN4
Human Protein:
UniProt O15554
Tissue:
Widely expressed in non-excitable tissues (absent in brain, skeletal muscle and heart), expressed in T and B lymphocytes, erythrocytes, Macrophages and monocytes
Function/ Application:
Immune regulation, cellular signalling, volume regulation in erythrocytes, involved in fluid and salt transport in secretory epithelia
Pathology:
Dehydrated hereditary stomatocytosis 2 (DHS2), hereditary xerocytosis, Diamond-Blackfan anemia, Sickle cell anemia,
Pharmacology:
As an inflammation-relevant drug target, KCa3.1 modulators are being investigated for potential in the treatment of asthma and fibroproliferative disorders, and for immunosuppressant efficacy.
Interaction:
Calmodulin, nucleoside diphosphate kinase B (NDPK-B)
Modulator:
Clotrimazole, charybdotoxin, riluzole, nitrendipine, TRAM-34
Assays:
Patch clamp
Recommended Reviews:
Kaczmarek et al. (2017) International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels. Pharmacol Rev 69(1):1-11
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