KCa1.1 | BK | Maxi-K | Calcium-activated Potassium Channel Subunit Alpha-1
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.
KCa1.1 Background Information
The KCa1.1 potassium channel (aka BK channel, Slo1 or Maxi-K channel) contributes to repolarization of the membrane potential. These channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. The channels are activated by both membrane depolarization or increase in cytosolic Ca2+ that mediates export of K+. It is also activated by the concentration of cytosolic Mg2+. The channels can be formed by 2 subunits: the pore-forming alpha subunit, which is the product of this gene, and the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits.
Gene:
KCNMA1
Human Protein:
UniProt Q12791
Tissue:
Widely expressed in all tissues, except myocytes
Function/ Application:
Controls excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity.
Pathology:
Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy (PNKD3), Cerebellar Atrophy, Developmental Delay, Dyskinesia, Chorea, Absence seizures
Pharmacology:
KCa1.1 channels are pharmacological targets for the treatment of stroke.
Interaction:
RAB11B, beta subunits: KCNMB1, KCNMB2, KCNMB3 and KCNMB4, gamma subunits: LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma subunits are accessory, and modulate its activity.
Modulator:
Tetraethylammonium (TEA), paxilline, iberiotoxin, hydrochlorothiazide, diazoxide, chlorzoxazone, cromoglicic acid, BMS 191011
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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