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Gene Review

Kcnn3  -  potassium channel, calcium activated...

Rattus norvegicus

Synonyms: KCa2.3, SK3, SKCa 3, SKCa3, Small conductance calcium-activated potassium channel protein 3
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Disease relevance of Kcnn3

  • SK3 immunoreactivity was detectable in hepatocytes in rat liver and in HTC rat hepatoma cells [1].
  • Among dorsal root ganglion neurons, both peripherin-positive (C-type) and peripherin-negative (A-type) cells show intense SK3 immunoreactivity [2].

High impact information on Kcnn3

  • These results demonstrate interactions that cause changes in protein trafficking, cell surface expression, and channel pharmacology and strongly suggest heteromeric assembly of SK3 with the other SK channel subunits [3].
  • In contrast to SK2, the SK3 subunit was detected neither in the developing nor in the adult retina [4].
  • Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system [5].
  • Double staining for oxytocin or vasopressin neurons revealed weak co-localization with SK3 but strong staining surrounding each neuron type [6].
  • Electron microscopy showed that SK3-like immunoreactivity was intense between neuronal somata and dendrites, in apparent glial processes, but weak in neurons [6].

Biological context of Kcnn3

  • Human embryonic kidney (HEK-293) cells transfected with liver SK3 expressed 10 pS K+ channels that were Ca2+ dependent (EC(50) 630 nM) and were blocked by the SK channel inhibitor apamin (IC(50) 0.6 nM); whole cell SK3 currents inactivated at membrane potentials more positive than -40 mV [1].
  • 4. In phenylephrine-preconstricted CA, acetylcholine-induced NO and prostacyclin-independent vasodilation was almost completely blocked by ChTX, CLT, TRAM-34, or TRAM-39 in combination with the SK3-blocker apamin [7].
  • A 33 bp sequence adjacent to the promoter was shown to act as an enhancer in L6 cells that express SK3 and estrogen receptor alpha (ER alpha) [8].
  • The data suggest that estrogen regulates SK3 gene expression through interactions between ER alpha and Sp1 [8].

Anatomical context of Kcnn3

  • Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract [9].
  • Immunoelectron microscopic analysis indicates that SK3 channels are localized on processes of ICC that are located close to the myenteric plexus between the longitudinal and circular muscle layers and within the muscular layers [9].
  • In rats and wild-type mice, SK3 immunostaining revealed an intense lacy network surrounding SON neurons, with weak staining in neuronal somata and dendrites [6].
  • These studies suggest a prominent role of SK3 channels in astrocytes [6].
  • Regional distribution of SK3 mRNA-containing neurons in the adult and adolescent rat ventral midbrain and their relationship to dopamine-containing cells [10].

Associations of Kcnn3 with chemical compounds

  • The sequence of the rat liver isoform differs from rat brain SK3 in five amino acid residues in the NH3 terminus, where it more closely resembles human brain SK3 [1].
  • To determine the distribution of SK3 channels within the SON, we used immunocytochemistry in rats and in transgenic mice with a regulatory cassette on the SK3 gene, allowing regulated expression with dietary doxycycline (DOX) [6].
  • SK3 small conductance, calcium-activated potassium channels play an important role in regulating the activity of mesencephalic dopamine (DA) neurons [10].
  • In denervated muscle fibers, SK3 is localized in the extrajunctional as well as the junctional plasma membrane, where it appears to be less abundant in the acetylcholine receptor-rich domains, corresponding to the crests of the postsynaptic folds [11].
  • Interestingly, expression of ER alpha in Cos7 cells and E2 treatment was sufficient to induce expression of the endogenous SK3 gene [8].

Other interactions of Kcnn3


Analytical, diagnostic and therapeutic context of Kcnn3

  • Using confocal microscopy and SK3 specific antibodies, we demonstrate that SK3 immunoreactivity is present at the rat neuromuscular junction in denervated but also in innervated muscles [11].
  • Since SK3 only has been shown to be expressed in muscles upon denervation, this channel may be involved in hyperexcitability and afterhyperpolarization observed in muscle cells in the absence of the nerve [11].
  • In addition, the expression of BK channels and SK3 subunits of SK channels was studied using double immunofluorescence detection [12].


  1. Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3. Barfod, E.T., Moore, A.L., Lidofsky, S.D. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  2. A functional role for small-conductance calcium-activated potassium channels in sensory pathways including nociceptive processes. Bahia, P.K., Suzuki, R., Benton, D.C., Jowett, A.J., Chen, M.X., Trezise, D.J., Dickenson, A.H., Moss, G.W. J. Neurosci. (2005) [Pubmed]
  3. The SK3 subunit of small conductance Ca2+-activated K+ channels interacts with both SK1 and SK2 subunits in a heterologous expression system. Monaghan, A.S., Benton, D.C., Bahia, P.K., Hosseini, R., Shah, Y.A., Haylett, D.G., Moss, G.W. J. Biol. Chem. (2004) [Pubmed]
  4. Developmental expression of the small-conductance Ca(2+)-activated potassium channel SK2 in the rat retina. Klöcker, N., Oliver, D., Ruppersberg, J.P., Knaus, H.G., Fakler, B. Mol. Cell. Neurosci. (2001) [Pubmed]
  5. Differential distribution of three Ca(2+)-activated K(+) channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Stocker, M., Pedarzani, P. Mol. Cell. Neurosci. (2000) [Pubmed]
  6. Immunocytochemical localization of small-conductance, calcium-dependent potassium channels in astrocytes of the rat supraoptic nucleus. Armstrong, W.E., Rubrum, A., Teruyama, R., Bond, C.T., Adelman, J.P. J. Comp. Neurol. (2005) [Pubmed]
  7. Selective blockade of endothelial Ca2+-activated small- and intermediate-conductance K+-channels suppresses EDHF-mediated vasodilation. Eichler, I., Wibawa, J., Grgic, I., Knorr, A., Brakemeier, S., Pries, A.R., Hoyer, J., Köhler, R. Br. J. Pharmacol. (2003) [Pubmed]
  8. Determinants contributing to estrogen-regulated expression of SK3. Jacobson, D., Pribnow, D., Herson, P.S., Maylie, J., Adelman, J.P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  9. Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract. Fujita, A., Takeuchi, T., Saitoh, N., Hanai, J., Hata, F. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  10. Regional distribution of SK3 mRNA-containing neurons in the adult and adolescent rat ventral midbrain and their relationship to dopamine-containing cells. Sarpal, D., Koenig, J.I., Adelman, J.P., Brady, D., Prendeville, L.C., Shepard, P.D. Synapse (2004) [Pubmed]
  11. Presynaptic localization of the small conductance calcium-activated potassium channel SK3 at the neuromuscular junction. Roncarati, R., Di Chio, M., Sava, A., Terstappen, G.C., Fumagalli, G. Neuroscience (2001) [Pubmed]
  12. Contribution of Ca2+-activated K+ channels to hyperpolarizing after-potentials and discharge pattern in rat supraoptic neurones. Greffrath, W., Magerl, W., Disque-Kaiser, U., Martin, E., Reuss, S., Boehmer, G. J. Neuroendocrinol. (2004) [Pubmed]
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