KCa4.1 | KNa1.1 | Slo2.2 | Potassium channel subfamily T member 1
Calcium- and sodium-activated Potassium channels
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
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.
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.
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.
Highest expression in liver, brain and spinal cord, further expression in in skeletal muscle
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
Epileptic encephalopathy, early infantile, 14 (EIEE14), Epilepsy, nocturnal frontal lobe, 5 (ENFL5), cardiac arrhythmia. West syndrome, Ohtahara syndrome, leukodystrophy and leukoencephalopathy
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
Niclosamide, loxapine, quinidine, bithionol, bepridil, clofilium, tetraethylammonium, SKA 31
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