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Gene Review

KCNN1  -  potassium channel, calcium activated...

Homo sapiens

Synonyms: KCa2.1, SK, SK1, SKCA1, SKCa 1, ...
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Disease relevance of KCNN1


Psychiatry related information on KCNN1

  • The potential value of pharmacological SK channel modulation in various pathological states such as increased epileptiform activity, cognitive impairment, pain, mood disorders and schizophrenia will be discussed [3].

High impact information on KCNN1

  • The predicted amino acid sequence is related to, but distinct from, the small conductance calcium-activated potassium channel subfamily, which is approximately 50% conserved. hIK1 mRNA was detected in peripheral tissues but not in brain [4].
  • Here we investigated which parts of the channels outside the pore region are important for apamin sensitivity by constructing chimeras between apamin-insensitive and -sensitive SK channel subunits and by introducing point mutations [5].
  • This finding hinted at the involvement of regions beyond the pore as determinants of apamin sensitivity, because hSK1 and rSK1 have an identical amino acid sequence in the pore region [5].
  • Three amino acids located in the outer vestibule of the pore are of particular importance for the different apamin sensitivities of SK channels [5].
  • Autophagy was blocked in the presence of dimethylsphingosine, an inhibitor of SK activity, and in cells expressing a catalytically inactive form of SK1 [6].

Biological context of KCNN1

  • Here we describe the gene structure of KCNN1 and its localization by radiation hybrid mapping to chromosome 19p13.1 [7].
  • Calcium-activated potassium ion channels SK and IK (small and intermediate conductance, respectively) may be important in the pathophysiology of pain following nerve injury, as SK channels are known to impose a period of reduced excitability after each action potential by afterhyperpolarization [8].
  • Small-conductance Ca2+-activated K+ channels (SK channels, KCa channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ with membrane potential [9].
  • To examine this issue, we have used the acute hippocampal slice model of epileptiform activity to investigate the effects of an enhancer of SK channel activity, 1-ethyl-benzimidazolinone (EBIO) [10].
  • We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats [11].

Anatomical context of KCNN1

  • We studied the presence and changes of human SK1 (hSK1)- and hIK1-like immunoreactivity in control and injured human dorsal root ganglia (DRG) and peripheral nerves and their regulation by key neurotrophic factors in cultured rat sensory neurones [8].
  • Because of the marked differential expression of SK channel isoforms in heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes [9].
  • Maurotoxin did inhibit (86)Rb efflux (IC(50), 45 nM) through, and (125)I-apamin binding (K(i), 10 nM) to SK channels in low ionic strength buffers (i.e., 18 mM sodium, 250 mM sucrose), which is consistent with previous reports of inhibition of apamin binding to brain synaptosomes [12].
  • 2. The whole-cell patch-clamp technique was used to measure K+ currents in dissociated adult ovine chromaffin cells as well as SK channel currents expressed in the H4IIE cell line [13].
  • Oxygen-sensing pathway for SK channels in the ovine adrenal medulla [13].

Associations of KCNN1 with chemical compounds

  • However, despite the presence of transcripts for IK and SK, neither clotrimazole, an inhibitor of IK channels, nor apamin, known to block most SK channels inhibited any current [14].
  • The SK channel opener 1-EBIO could still produce channel activation in the presence of apamin [15].
  • The effects of fluoxetine (Prozac) on the activity of human small-conductance calcium-activated potassium (SK) channels were investigated utilizing a functional fluorescence assay with bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC(4)(3)) [16].
  • Furthermore, its inhibitory effect in the full disinhibition model of epileptiform activity (10 microM gabazine + 10 microM CGP55845) was occluded by the SK channel blocker apamin (300 nM-1 microM) which in its own right increased the duration and reduced the frequency of individual epileptiform bursts [10].
  • Peptide toxins such as apamin and scyllatoxin, as well as organic compounds such as quaternary salts of bicuculline, dequalinium, UCL 1684 and UCL 1848 serve as non-specific SK channel blockers [3].

Other interactions of KCNN1


Analytical, diagnostic and therapeutic context of KCNN1

  • In addition, using Western blotting, we sought to determine the level of protein expression of SK and IK channels in sensory nervous tissues following induction of inflammation (Freund's Complete Adjuvant (FCA) arthritis model) or nerve injury (chronic constriction injury model) [20].
  • The genetic similarity of different generations of Neocallimastix frontalis SK was examined by random amplified polymorphic DNA (RAPD) profiling and internal transcribed spacer 1 (ITS1) sequence analysis [21].


  1. Calmodulin binding to the C-terminus of the small-conductance Ca2+-activated K+ channel hSK1 is affected by alternative splicing. Zhang, B.M., Kohli, V., Adachi, R., López, J.A., Udden, M.M., Sullivan, R. Biochemistry (2001) [Pubmed]
  2. Expression and distribution of a small-conductance calcium-activated potassium channel (SK3) protein in skeletal muscles from myotonic muscular dystrophy patients and congenital myotonic mice. Kimura, T., Takahashi, M.P., Fujimura, H., Sakoda, S. Neurosci. Lett. (2003) [Pubmed]
  3. Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Blank, T., Nijholt, I., Kye, M.J., Spiess, J. Current drug targets. CNS and neurological disorders. (2004) [Pubmed]
  4. A human intermediate conductance calcium-activated potassium channel. Ishii, T.M., Silvia, C., Hirschberg, B., Bond, C.T., Adelman, J.P., Maylie, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. An Amino Acid Outside the Pore Region Influences Apamin Sensitivity in Small Conductance Ca2+-activated K+ Channels. Nolting, A., Ferraro, T., D'hoedt, D., Stocker, M. J. Biol. Chem. (2007) [Pubmed]
  6. Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation. Lavieu, G., Scarlatti, F., Sala, G., Carpentier, S., Levade, T., Ghidoni, R., Botti, J., Codogno, P. J. Biol. Chem. (2006) [Pubmed]
  7. Gene structure and chromosome mapping of the human small-conductance calcium-activated potassium channel SK1 gene (KCNN1). Litt, M., LaMorticella, D., Bond, C.T., Adelman, J.P. Cytogenet. Cell Genet. (1999) [Pubmed]
  8. Calcium-activated potassium channel SK1- and IK1-like immunoreactivity in injured human sensory neurones and its regulation by neurotrophic factors. Boettger, M.K., Till, S., Chen, M.X., Anand, U., Otto, W.R., Plumpton, C., Trezise, D.J., Tate, S.N., Bountra, C., Coward, K., Birch, R., Anand, P. Brain (2002) [Pubmed]
  9. Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Tuteja, D., Xu, D., Timofeyev, V., Lu, L., Sharma, D., Zhang, Z., Xu, Y., Nie, L., Vázquez, A.E., Young, J.N., Glatter, K.A., Chiamvimonvat, N. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  10. Activation of SK channels inhibits epileptiform bursting in hippocampal CA3 neurons. Lappin, S.C., Dale, T.J., Brown, J.T., Trezise, D.J., Davies, C.H. Brain Res. (2005) [Pubmed]
  11. Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder? Chandy, K.G., Fantino, E., Wittekindt, O., Kalman, K., Tong, L.L., Ho, T.H., Gutman, G.A., Crocq, M.A., Ganguli, R., Nimgaonkar, V., Morris-Rosendahl, D.J., Gargus, J.J. Mol. Psychiatry (1998) [Pubmed]
  12. Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Castle, N.A., London, D.O., Creech, C., Fajloun, Z., Stocker, J.W., Sabatier, J.M. Mol. Pharmacol. (2003) [Pubmed]
  13. Oxygen-sensing pathway for SK channels in the ovine adrenal medulla. Keating, D.J., Rychkov, G.Y., Giacomin, P., Roberts, M.L. Clin. Exp. Pharmacol. Physiol. (2005) [Pubmed]
  14. Expression and function of calcium-activated potassium channels in human glioma cells. Weaver, A.K., Bomben, V.C., Sontheimer, H. Glia (2006) [Pubmed]
  15. Partial apamin sensitivity of human small conductance Ca2+-activated K+ channels stably expressed in Chinese hamster ovary cells. Dale, T.J., Cryan, J.E., Chen, M.X., Trezise, D.J. Naunyn Schmiedebergs Arch. Pharmacol. (2002) [Pubmed]
  16. The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3. Terstappen, G.C., Pellacani, A., Aldegheri, L., Graziani, F., Carignani, C., Pula, G., Virginio, C. Neurosci. Lett. (2003) [Pubmed]
  17. Interactions of N-Terminal and C-Terminal Parts of the Small Conductance Ca Activated K(+) Channel, hSK3. Frei, E., Spindler, I., Grissmer, S., Jager, H. Cell. Physiol. Biochem. (2006) [Pubmed]
  18. Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1. Wulff, H., Gutman, G.A., Cahalan, M.D., Chandy, K.G. J. Biol. Chem. (2001) [Pubmed]
  19. No evidence for involvement of KCNN3 (hSKCa3) potassium channel gene in familial and isolated cases of schizophrenia. Bonnet-Brilhault, F., Laurent, C., Campion, D., Thibaut, F., Lafargue, C., Charbonnier, F., Deleuze, J.F., Ménard, J.F., Jay, M., Petit, M., Frebourg, T., Mallet, J. Eur. J. Hum. Genet. (1999) [Pubmed]
  20. The distribution of small and intermediate conductance calcium-activated potassium channels in the rat sensory nervous system. Mongan, L.C., Hill, M.J., Chen, M.X., Tate, S.N., Collins, S.D., Buckby, L., Grubb, B.D. Neuroscience (2005) [Pubmed]
  21. The genetic similarity of different generations of Neocallimastix frontalis SK. Chen, Y.C., Hseu, R.S., Cheng, K.J. FEMS Microbiol. Lett. (2003) [Pubmed]
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