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: K_Ca1.1 (also known as BK or Maxi-K), K_Ca2.1 (also known as SK1), K_Ca2.2 (also known as SK2), K_Ca2.3 (also known as SK3) , K_Ca3.1 (also known as IK or SK4), K_Ca4.1, K_Ca4.2, K_Ca5.1

Topology:
K_Ca 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 K_Ca4 and K_Ca5 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 K_Ca4.1 channel aka K_Na1.1, 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 K_Na1.1 forms tetramers with K_Na1.2., 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

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.