KCa2.1 channels
| Channel name | KCa2.1 |
| Description | Small-conductance, calcium-activated potassium channel; activated via a calmodulin-dependent mechanism |
| Other names | SK11,2, SKCa1 |
| Molecular information | Human: 543aa, NM_002248, chr. 19p13.1,3 KCNN1 |
| Mouse: 580aa, NM_032397, chr. 8 | |
| Rat: 536aa, NM_019313, chr. 16p14 | |
| Associated subunits | Calmodulin tightly complexed to C terminus4 |
| Functional assays | Electrophysiology |
| Current | Small-conductance, calcium-activated K+ current in neurones1 |
| Conductance | 9.2pS (symmetric K+), 2–3pS (normal Ringer) |
| Ion selectivity | K+-selective |
| Activation | Activated by intracellular Ca2+ (Kd = 0.7 μM, nH = 4)4 |
| Inactivation | None |
| Activators | Ca2+, EBIO (630 μM),5 NS309 (30 nM),6 riluzole (2 μM) |
| Gating inhibitors | None |
| Blockers | UCL1684 (1 nM),7 apamin (8 nM),8 tamapin (42 nM),9 leiurotoxin/scyllatoxin (325 nM),10 dequalinium (400 nM), leiurotoxin-Dab7 (6 μM),10 fluoxetine (7 μM), tubocurarine (23 μm), biciculline (1.1 μM)14 |
| Radioligands | [125I]apamin11 |
| Channel distribution | Brain (amygdala > hippocampus, caudate nucleus, foetal brain > cerebellum > thalamus, substantia nigra, spinal cord, pituitary gland), oligodendroglioma, glioblastoma, gastric tumour, aorta4,12 |
| Physiological functions | Involved in the afterhyperpolarization in vertebrate neurones |
| Mutations and pathophysiology | Not established |
| Pharmacological significance | Modulators of SK channel subtypes may have potential use in the treatment of myotonic muscular dystrophy, gastrointestinal dysmotility, memory disorders, epilepsy narcolepsy, and alcohol intoxication13 |
| Comments | Channel is voltage-independent and weakly rectifying; intron-exon structure of KCa2.1–KCa2.3 (SK) and KCa3.1 (IK) genes are conserved |
aa, amino acids; chr., chromosome; NS309, 6,7-dichloro-1H-indole-2,3-dione-3-oxime; SK, small-conductance K+ channel; IK, intermediate-conductance K+ channel; EBIO, 1-ethyl-2-benzimidazolinone; UCL1684, 6,12,19,20,25,26-hexahycro-5,27:13,18:21,24-trietheno-11,7-methano-7H-dibenzo[b,n] [1,5,12,16] tetraazacyclotricosine-5,13-dilum ditrifluoroacetate.
↵1. Kohler M, Hirschberg B, Bond CT, Kinzie JM, Marrion NV, Maylie J, and Adelman JP (1996) Small-conductance, calcium-activated potassium channels from mammalian brain. Science 273:1709-1714
↵2. Litt M, LaMorticella D, Bond CT, and Adelman JP (1999) Gene structure and chromosome mapping of the human small-conductance calcium-activated potassium channel SK1gene (KCNN1). Cytogenet Cell Genet 86:70-73
↵3. Ghanshani S, Wulff H, Miller MJ, Rohm H, Neben A, Gutman GA, Cahalan MD, and Chandy KG (2000) Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences. J Biol Chem 275:37137-37149
↵4. Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE, Ishii T, Hirschberg B, Bond CT, Lutsenko S, et al. (1998) Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature (Lond) 395:503-507
↵5. Dale TJ, Cryan JE, Chen MX, Trezise DJ (2002) Partial apamin sensitivity of human small conductance Ca2+-activated K+ channels stable expressed in Chinese hamster ovary cells. Naunyn Schmiedeberg's Arch Pharmacol 366:470-477
↵6. Strobaek D, Teuber L, Jorgensen TD, Ahring PK, Kaer K, Hansen RS, Olesen SP, Christophersen P, and Skaaning-Jensen B (2004) Activation of human IK and SK Ca2+-activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime). Biochim Biophys Acta 1665:1-5
↵7. Strobaek D, Jorgensen TD, Christophersen P, Ahring PK, and Olesen S-P (2000) Pharmacological characterization of small-conductance Ca2+-activated K+ channels stably expressed in HEK 293 cells. Br J Pharmacol 129:991-999
↵8. Shah M and Haylett DG (2000) The Pharmacology of hSK1 Ca2+-activated K+ channels expressed in mammalian cell lines. Br J Pharmacol 129:627-630
↵9. Pedarzani P, D'hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jeyaseelan K, Kini RM, Gadre SV, Sapatnekar SM, Stocker M, et al. (2002) Tamapin, a venompeptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and after hyperpolarization currents in central neurons. J Biol Chem 277:46101-46109
↵10. Shakkottai VG, Regaya I, Wulff H, Fajloun Z, Tomita H, Fathallah M, Cahalan MD, Gargus JJ, Sabatier JM, and Chandy KG (2001) Design and characterization of a highly selective peptide inhibitor of the small conductance calcium-activated K+ channel, SKCa2. J Biol Chem 276:43145-43151
↵11. Romey G, Hugues M, Schmid-Antomarchi H, and Lazdunski M (1984) Apamin: a specific toxin to study a class of Ca2+-dependent K+ channels. J Physiol (Paris) 79:259-264
↵12. Stocker M and Pedarzani P (2000) Differential distribution of three Ca2+-activated K+ channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Mol Cell Neurosci 15:476-493
↵13. Coghlan MJ, Carrol WA, and Gopalakrishnan M (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J Med Chem 44:1-27
↵14. Khawaled R, Bruening-Wright A, Adelman JP, and Maylie J (1999) Bicuculline block of small-conductance calcium-activated potassium channels. Pflugers Arch Eur J Physiol 438:314-321