• KCa1.1

    Single channel currents of BK channels as recorded from CHO cells in the cell attached mode on the Port-a-Patch

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

icon pap   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

application kca11 1

icon pap   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

icon pap   Port-a-Patch data and applications:p24 2 InternalApp

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) - Activation by Internal Calcium

BK verticalicon pl   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

Icon N1   SURFE²R N1 and   icon sp96   SyncroPatch 96 (a predecessor model of the SyncroPatch 384PE) and   icon pap   Port-a-Patch poster, GRC - Organellar Channels and Transporters 2015   logo pdf   (1.6 MB)

Publications

2019 - KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis

icon pap   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

icon pap   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

icon pap   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.

2014 - Multi-Generational Pharmacophore Modeling for Ligands to the Cholane Steroid-Recognition Site in the β1 Modulatory Subunit of the BK(Ca) Channel

icon pl  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

icon pap  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.

2009 - Robotic multiwell planar patch-clamp for native and primary mammalian cells

icon pl  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

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Small Journal (2006)

Authors: 
Brüggemann A., Stoelzle S., George M., Behrends J.C., Fertig N.

 

 

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