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Gene Review

Kcnn3  -  potassium intermediate/small conductance...

Mus musculus

Synonyms: KCa2.3, SK3, SKCA3, SKCa 3, SKCa3, ...
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Disease relevance of Kcnn3


High impact information on Kcnn3

  • The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function [1].
  • Here we show that elevated expression of small-conductance Ca2+-activated K+ channels (SK channels) of the SK3 type in hippocampi of aged mice contributes to reduced long-term potentiation (LTP) and impaired trace fear conditioning, a hippocampus-dependent learning task [3].
  • In the tTA-SK3 tet-off mouse, a normal amount of SK3 protein was present in islets, but it became undetectable after exposure to doxycycline (DOX), which inhibits the transcription of the tTA-SK3 gene [4].
  • In SK3-tTA tet-off mice, the addition of apamin with glucose and tetraethylammonium (TEA) caused a similar elevation in [Ca(2+)](i), which was greatly diminished after DOX suppression of SK3 expression [4].
  • AZ inhibition of K(slow) also supported mediation by SK, rather than cardiac-like slow delayed rectifier channels since bath application of AZ to HEK 293 cells expressing SK3 cDNA reduced SK current [5].

Biological context of Kcnn3

  • Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3 [1].
  • Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure [6].
  • In intact arteries, SK3 channels contributed to sustained hyperpolarization of the endothelial membrane potential, which was communicated to the arterial smooth muscle [6].
  • These results indicate expression of SK3 in fibroblast-like cells, but not in ICC, and suggest participation of the cells in the intestinal motility [7].

Anatomical context of Kcnn3


Associations of Kcnn3 with chemical compounds

  • To investigate the role of SK3 channels in denervation- induced hyperexcitability, SK3 expression was manipulated using a transgenic mouse that harbors a tetracycline-regulated SK3 gene [12].

Other interactions of Kcnn3

  • Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P<0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls [13].
  • Studies of SK channel knock-out mice reveal that of the three apamin-sensitive SK channel subunits (SK1-SK3), only SK2 subunits are necessary for the apamin-sensitive currents in CA1 hippocampal neurons [14].

Analytical, diagnostic and therapeutic context of Kcnn3

  • SK3 was detected in the endothelium and not in the smooth muscle by immunohistochemistry [6].
  • Quantification of SK1, SK2, and SK3 transcripts between atria and ventricles was performed using real-time quantitative RT-PCR from single, isolated cardiomyocytes [15].
  • Because this expression pattern suggested a presynaptic localization, we examined the subcellular distribution of SK3 in cultured hippocampal neurons using high-resolution immunofluorescence analysis [16].
  • Expression of SK3, a small conductance Ca(2+)-activated K(+) channel (SK channel) in skeletal muscle is induced by denervation, and direct application of apamin, a peptide blocker of SK channels, dramatically reduces hyperexcitability [12].


  1. Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. Bond, C.T., Sprengel, R., Bissonnette, J.M., Kaufmann, W.A., Pribnow, D., Neelands, T., Storck, T., Baetscher, M., Jerecic, J., Maylie, J., Knaus, H.G., Seeburg, P.H., Adelman, J.P. Science (2000) [Pubmed]
  2. A monoclonal antibody reactive with Marek's disease tumor-associated surface antigen. Lee, L.F., Liu, X., Sharma, J.M., Nazerian, K., Bacon, L.D. J. Immunol. (1983) [Pubmed]
  3. Small-conductance, Ca2+-activated K+ channel SK3 generates age-related memory and LTP deficits. Blank, T., Nijholt, I., Kye, M.J., Radulovic, J., Spiess, J. Nat. Neurosci. (2003) [Pubmed]
  4. Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses. Tamarina, N.A., Wang, Y., Mariotto, L., Kuznetsov, A., Bond, C., Adelman, J., Philipson, L.H. Diabetes (2003) [Pubmed]
  5. Pharmacological properties and functional role of Kslow current in mouse pancreatic beta-cells: SK channels contribute to Kslow tail current and modulate insulin secretion. Zhang, M., Houamed, K., Kupershmidt, S., Roden, D., Satin, L.S. J. Gen. Physiol. (2005) [Pubmed]
  6. Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure. Taylor, M.S., Bonev, A.D., Gross, T.P., Eckman, D.M., Brayden, J.E., Bond, C.T., Adelman, J.P., Nelson, M.T. Circ. Res. (2003) [Pubmed]
  7. Localization of Ca2+-activated K+ channel, SK3, in fibroblast-like cells forming gap junctions with smooth muscle cells in the mouse small intestine. Fujita, A., Takeuchi, T., Jun, H., Hata, F. J. Pharmacol. Sci. (2003) [Pubmed]
  8. Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain. Sailer, C.A., Kaufmann, W.A., Marksteiner, J., Knaus, H.G. Mol. Cell. Neurosci. (2004) [Pubmed]
  9. Molecular properties of small-conductance Ca2+-activated K+ channels expressed in murine colonic smooth muscle. Ro, S., Hatton, W.J., Koh, S.D., Horowitz, B. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  10. Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel. Herrera, G.M., Pozo, M.J., Zvara, P., Petkov, G.V., Bond, C.T., Adelman, J.P., Nelson, M.T. J. Physiol. (Lond.) (2003) [Pubmed]
  11. Two pathways for the activation of small-conductance potassium channels in neurons of substantia nigra pars reticulata. Yanovsky, Y., Zhang, W., Misgeld, U. Neuroscience (2005) [Pubmed]
  12. SK channels are necessary but not sufficient for denervation-induced hyperexcitability. Jacobson, D., Herson, P.S., Neelands, T.R., Maylie, J., Adelman, J.P. Muscle Nerve (2002) [Pubmed]
  13. Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse. Ding, H., Hashem, M., Wiehler, W.B., Lau, W., Martin, J., Reid, J., Triggle, C. Br. J. Pharmacol. (2005) [Pubmed]
  14. Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity. Hammond, R.S., Bond, C.T., Strassmaier, T., Ngo-Anh, T.J., Adelman, J.P., Maylie, J., Stackman, R.W. J. Neurosci. (2006) [Pubmed]
  15. 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]
  16. The small conductance Ca2+-activated K+ channel SK3 is localized in nerve terminals of excitatory synapses of cultured mouse hippocampal neurons. Obermair, G.J., Kaufmann, W.A., Knaus, H.G., Flucher, B.E. Eur. J. Neurosci. (2003) [Pubmed]
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