Skip to main content
SpringerLink
Log in

Reciprocal regulation of expression of pore‐forming KATP channel genes by hypoxia

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The ATP‐sensitive potassium (KATP) channel is thought to play an important role in the protection of heart and brain against tissue hypoxia. The genetic regulation of the components of the channel by hypoxia has not been previously described. Here, we investigated the regulation of the two pore‐forming channel proteins, Kir6.1 and Kir6.2, in response to hypoxia in vivo and in vitro. We find that these two structurally‐related inwardly-rectifying potassium channel proteins are reciprocally regulated by hypoxia in vivo, with upregulation of Kir6.1 and down‐regulation of Kir6.2, thereby resulting in a significant change in the composition of the channel complex in response to hypoxia. In vitro we describe neuronal and cardiac cell lines in which Kir6.1 is up‐regulated by hypoxia, demonstrating that Kir6.1 is a hypoxia‐inducible gene. We conclude that the heart and brain display genetic plasticity in response to hypoxic stress through specific genetic reprograming of cytoprotective channel genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bunn F, Poyton RO: Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76: 839–885, 1996

    Google Scholar 

  2. Levy AP: Regulation of gene expression by hypoxia. In: N. Sperelakis, Y. Kurachi, A. Terzic, M.V. Cohen (eds). Heart Physiology and Pathophysiology, 4th edn. Academic Press, San Diego, 2001, pp 1225–1233

    Google Scholar 

  3. Acker H: Cellular oxygen sensors. Ann NY Acad Sci 718: 3–10, 1994

    Google Scholar 

  4. Wang GL, Semenza GL: General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA 90: 4304–4308, 1993

    Google Scholar 

  5. Noma A: ATP regulated K channels in cardiac muscle. Nature 305: 147–148, 1983

    Google Scholar 

  6. Dzeja PP, Terzic A: Phosphotransfer reactions in the regulation of ATPsensitive K channels. FASEB J 12: 523–529, 1998

    Google Scholar 

  7. Jovanovic A, Jovanovic S, Carrasco AJ, Terzic A: Acquired resistance of a mammalian cell line to hypoxia-reoxygenation through cotransfection of Kir6.2 and SUR1 clones. Lab Invest 78: 1101–1107, 1998

    Google Scholar 

  8. Jovanovic N, Jovanovic S, Jovanovic A, Terzic A: Gene delivery of Kir6.2/SUR2A in conjunction with pinacidil handles intracellular Ca homeostasis under metabolic stress. FASEB J 13: 923–929, 1999

    Google Scholar 

  9. Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J: A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K channels. Science 270: 1166–1170, 1995

    Google Scholar 

  10. Inagaki N, Tsuura Y, Namba N, Masuda K, Gonoi T, Horie M, Seino Y, Mizuta M, Seino S: Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle and heart. J Biol Chem 270: 5691–5694, 1995

    Google Scholar 

  11. Seino S: ATP sensitive potassium channels: A model of heteromultimeric potassium channel/receptor assemblies. Annu Rev Physiol 61: 337–362, 1999

    Google Scholar 

  12. Clement JP, Kunjilwar K, Gonzalez G, Schwanstecher M, Panten U, Aguilar-Bryan L, Bryan J: Association and stoichiometry of K(ATP) channel subunits. Neuron 18: 827–838, 1997

    Google Scholar 

  13. Lorenz E, Alekseev AE, Krapivinsky G, Carrasco AJ, Clapham DE, Terzic A: Evidence for direct physical association between a K channel (Kir6.2) and an ATP binding cassette protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K channel. Mol Cell Biol 18: 1652–1659, 1998

    Google Scholar 

  14. Akao M, Sakurai T, Horie M, Otani H, Takanao M, Kouchi I, Murakami T, Sasayama S: Angiotensin II type I receptor blockade abolishes specific K(ATP) channel gene expression in rats with myocardial ischemia. J Mol Cell Cardiol 32: 2239–2247, 2000

    Google Scholar 

  15. Sgard F, Faure C, Drieu la Rochelle C, Graham D, O'Connor SE, Jania P, Besnard F: Regulation of ATP-sensitive potassium channel mRNA expression in rat kidney following ischemic injury. Biochem Biophys Res Commun 269: 618–622, 2000

    Google Scholar 

  16. Avivi A, Resnick MB, Nevo E, Joel A, Levy AP: Adaptive hypoxic tolerance in the subterranean mole rat Spalax ehrenbergi: The role of vascular endothelial growth factor. FEBS Lett 452/3: 133–140, 1999

    Google Scholar 

  17. Repunte VP, Nakamura H, Fujita A, Horio Y, Findlya I, Pott L, Kurachi Y: Extracellular links in Kir subunits control the unitary conductance of SUR/Kir6.0 ion channels. EMBO J 18: 3317–3324, 1999

    Google Scholar 

  18. Levy AP, Levy NS, Loscalzo J, Calderone A, Takahashi N, Yeo K, Koren G, Colucci WS, Goldberg MA: Regulation of vascular endothelial growth factor in cardiac myocytes. Circ Res 76: 758–766, 1995.

    Google Scholar 

  19. Ammala C, Moorhouse A, Gribble F, Ashfield R, Proks P, Smith PA, Sakura H, Coles B, Ashcroft SJ, Ashcroft FM: Promiscuous coupling between the sulphonylurea receptor and inwardly rectifying potassium channels. Nature 379: 545–548, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Technion‐Israel Institute of Technology, Haifa, Israel, 31096

    Meira Melamed‐Frank & Andrew P. Levy

  2. Mayo Clinic, Rochester, Minnesota, 55905, USA

    Andre Terzic & Antonio J. Carrasco

  3. Institute of Evolution, University of Haifa, Haifa, Israel, 31999

    Eviatar Nevo & Aaron Avivi

Authors
  1. Meira Melamed‐Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Terzic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio J. Carrasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eviatar Nevo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aaron Avivi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew P. Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew P. Levy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melamed‐Frank, M., Terzic, A., Carrasco, A.J. et al. Reciprocal regulation of expression of pore‐forming KATP channel genes by hypoxia. Mol Cell Biochem 225, 145–150 (2001). https://doi.org/10.1023/A:1012286624993

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012286624993

Search

Navigation