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