• KCa4.1

    Voltage-dependent outward current in WT and mutated KCA4.1 expressing cells, analyzed on the SyncroPatch 384PE

    Gertler T.S. et al. (2019)

     

KCa4.1 | KNa1.1 | Slo2.2 | Potassium channel subfamily T member 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.

KCa4.1 Background Information

The KCa4.1 channel aka KNa1.1, Slo2.2, is an outwardly rectifying potassium channel subunit that may assemble with other Slo-type channel units. It is activated by high intracellular sodium or chloride levels and upon stimulation of G-protein coupled receptors, such as CHRM1 and GRIA1.

Gene:
KCNT1

Human Protein:
UniProt Q5JUK3

Tissue:
Highest expression in liver, brain and spinal cord, further expression in in skeletal muscle

Function/ Application:
Regulating firing patterns of neurons, providing a major component of potassium currents in several types of central neurons, assisting apical absorption of Na+ and Cl- in transport epithelium

Pathology:
Epileptic encephalopathy, early infantile, 14 (EIEE14), Epilepsy, nocturnal frontal lobe, 5 (ENFL5), cardiac arrhythmia. West syndrome, Ohtahara syndrome, leukodystrophy and leukoencephalopathy

Interaction:
The Slack-B isoform of KNa1.1 forms tetramers with KNa1.2., FMR1 enhances channel opening, TMEM16C modulates channel currents and expression, interacts with CRBN

Modulator:
Niclosamide, loxapine, quinidine, bithionol, bepridil, clofilium, tetraethylammonium, SKA 31

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

Publications

2019 - Functional consequences of a KCNT1 variant associated with status dystonicus and early‐onset infantile encephalopathy

icon sp96   SyncroPatch 384PE (a predeccessor model of the SyncroPatch 384i) publication in Annals of Clinical and Translational Neurology (2019)

Authors:
Gertler T.S., Thompson C.H., Vanoye C.G., Millichap J.J., George Jr A.L.

 

 

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