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
Data and Applications
Neurons (Primary Hippocampal Granule Cell) - Current Traces
Port-a-Patch data and applications:
Recordings from acutely isolated hippocampal granule cells show BK- and CaV currents. Whole cell currents were obtained by depolarizing voltage pulses from a holding potential of −80 mV.
KCa1.1 (BK) - Single Channel Recordings
Port-a-Patch data and applications:
Single channel recordings of BK channels as recorded from CHO cells in the cell attached mode at +60 mV (top), +40 mV (middle) and 0 mV (lowest trace).
KCa1.1 (BK) - Intracellular Second Messengers
Port-a-Patch data and applications:
Currents mediated by BK channels expressed in CHO cells were studied using the Internal Perfusion System. Currents were elicited by a voltage step from -80 mV to +80 mV before and after adding an internal solution containing a higher concentration of free Ca2+.
KCa1.1 (BK) - High throughput study
SyncroPatch 384i (a predecessor model of SyncroPatch 384) data and applications:
Data kindly provided by Sharan R. Srinivasan1 and Vikram G. Shakkottai1,2
1Department of Neurology, University of Michigan, Ann Arbor, MI 48109;
2Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.
HEK293 cells stably transfected with BK channels were used to screen over 50,000 compounds, and using clever buffering techniques, targeting only activators of calcium sensitivity for BK channel augmentation.
KCa1.1 (BK) - Activation by Internal Calcium
Patchliner data and applications:
Top: BK (KCa1.1) current voltage relationships in a single cell showing effects of changing the intracellular free Ca2+ concentration (15 nM, n = 9; 108 nM, n = 11; 316 nM, n = 11).
Bottom: Comparison of BK (KCa1.1) current voltage relationships obtained on a conventional patch clamp setup (closed circles, n = 10) and on the Patchliner (open circles, n = 11).
Data are taken from Milligan C.J. et al., Nature Protocols, 2009, 4(2), 244-255.
Posters
2015 - Organellar Transporters and Ion Channels - How to access their electrophysiology by using the SURFE2R technology and Planar Patch Clamp
SURFE²R N1 and SyncroPatch 96 (a predecessor model of the SyncroPatch 384) and Port-a-Patch poster, GRC - Organellar Channels and Transporters 2015 
(1.6 MB)
Publications
2019 - KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis
Port-a-Patch publication in Arthritis Research & Therapy (2019)
Authors:
Tanner M.R., Pennington M.W., Chauhan S.S., Laragione T., Gulko P.S., Beeton C.
2019 - Inhibition of Polyamine Biosynthesis Reverses Ca2+ Channel Remodeling in Colon Cancer Cells
Port-a-Patch publication in Cancers (2019)
Authors:
Gutiérrez L.G., Hernández-Morales M., Núñez L., Villalobos C.
2018 - Targeting KCa1.1 channels with a scorpion venom peptide for the therapy of rat models of rheumatoid arthritis
Port-a-Patch publication in The Journal of Pharmacology and Experimental Therapeutics (2018)
Authors:
Tanner M.R., Pennington R.W., Chamberlain B.H., Huq R., Gehrmann E.J., Laragione, T., Gulko P.S., Beeton C.
2015 - Golgi anti-apoptotic proteins are highly conserved Ion Channels That Affect Apoptosis and Cell Migration
Port-a-Patch and 
Vesicle Prep Pro publication in Journal of Biological Chemistry (2015)
Authors:
Carrara G., Saraiva N., Parsons M., Byrne B., Prole D.L., Taylor C.W., Smith G.L.
2014 - Multi-Generational Pharmacophore Modeling for Ligands to the Cholane Steroid-Recognition Site in the β1 Modulatory Subunit of the BK(Ca) Channel
Patchliner publication in Journal of Molecular Graphics and Modelling (2014)
Authors:
McMillan J.E., Bukiya A.N., Terrell C.L., Patil S.A., Miller D.D., Dopico A.M., Parrilla A.L.
2014 - KCNMA1 Encoded Cardiac BK Channels Afford Protection against Ischemia-Reperfusion Injury
Port-a-Patch publication in PLoS One (2014)
Authors:
Soltysinska E., Bentzen B.H., Barthmes M., Hattel H., Thrush A.B., Harper M.E., Qvortrup K., Larsen F.J., Schiffer T.A., Losa-Reyna J., Straubinger J., Kniess A., Thomsen M.B., Brüggemann A., Fenske S., Biel M., Ruth P., Wahl-Schott C., Boushel R.C., Olesen S.P., Lukowski R.
2011 - Development of a selective small-molecule inhibitor of Kir1.1, the Renal Outer Medullary Potassium Channel
Patchliner publication in Molecular Pharmacology (2011)
Authors:
Bhave G., Chauder B.A., Liu W., Dawson E.S., Kadakia R., Nguyen T.T., Lewis L.M., Meiler J., Weaver C.D., Satlin L.M., Lindsley C.W., Denton J.S.
2009 - Robotic multiwell planar patch-clamp for native and primary mammalian cells
Patchliner publication in Nature Protocols (2009)
Authors:
Milligan C.J., Li J., Sukumar P., Majeed Y., Dallas M.L., English A., Emery P., Porter K.E., Smith A.M., McFadzean I., Beccano-Kelly D., Bahnasi Y., Cheong A., Naylor J., Zeng F., Liu X., Gamper N., Jiang L., Pearson H.A., Peers C., Robertson B., Beech D.J.
2006 - Microchip technology for automated and parallel patch clamp recording
Port-a-Patch and Patchliner publication in Small Journal (2006)
Authors:
Brüggemann A., Stoelzle S., George M., Behrends J.C., Fertig N.