Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News and Commentary
  • Published:

Stress without distress: homeostatic role for KATP channels

Molecular Psychiatry volume 8, pages 253–254 (2003)Cite this article

Stress is defined as a threat, real or implied, to the narrow range of physiological parameters necessary for survival, with the dynamic of existence comprising an ongoing sequence of stressful events and their consequences.1 Self-preservation is achieved through the general adaptation syndrome that is initiated by brain recognition of threat leading to modification of behavior and activation of the hypothalamic-pituitary–adrenal axis and autonomic nervous system.1 This ubiquitous response underlies the ‘fight-or-flight’ reaction by alteration of bodily functions to sustain a new performance level necessary for confrontation or evasion of threatening conditions.1 However, augmentation in performance is metabolically demanding, and requires a safety mechanism to prevent fatal exhaustion of resources. Recently, the ATP-sensitive potassium (KATP) channel, a cell membrane metabolic sensor, was identified as a critical component in maintaining the body's homeostasis during the adaptive reaction to stress, such that the reaction itself does not become deleterious to the organism.2

KATP channels, widely represented in metabolically active tissues, are formed through physical association of the pore-forming inwardly rectifying potassium channel, Kir6.x, with the regulatory sulfonylurea receptor, SUR.3 In this way, Kir6.2 and SUR2A generate cardiac and skeletal muscle KATP channels.4 Metabolic sensing occurs through modulation of Kir6.2 ATP-sensitivity by the SUR2A subunit ATPase activity such that stabilization of SUR2A in a posthydrolytic state favors K+ efflux through Kir6.2 leading to membrane hyperpolarization.5 These intrinsic channel properties, along with tight integration of KATP channel proteins with cellular metabolic pathways, are responsible for the rapid and precise metabolic modulation of membrane potential-dependent cellular functions.5 Vascular smooth muscle channels combine Kir6.1 and SUR2B,6 and channels in pancreatic β-cells comprise Kir6.2 and SUR1.3 In neurons, various permutations of Kir6.1 or Kir6.2 and SUR1 or SUR2 coexpression form KATP channels.7 Such structural diversity defines a wide spectrum of KATP channel involvement in tissue-specific functions, yet the underlying property of the metabolic mediator remains consistent.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Selye H . Stress Without Distress. New American Library: New York, 1974.

    Google Scholar 

  2. Zingman LV et al. Proc Natl Acad Sci USA 2002; 99: 13278–13283.

  3. Inagaki N et al. Science 1995; 270: 1166–1170.

  4. Inagaki N et al. Neuron 1996; 16: 1011–1017.

  5. Zingman LV et al. Neuron 2001; 31: 233–245.

  6. Yamada M et al. J Physiol 1997; 499: 715–720.

  7. Miki T et al. Nat Neurosci 2001; 4: 507–512.

  8. Miki T et al. Nat Med 2002; 8: 466–472.

  9. Ashcroft FM, Gribble FM . Trends Neurosci 1998; 21: 288–294.

  10. Koster JC et al. Cell 2000; 100: 645–654.

  11. Aguilar-Bryan L et al. Science 1995; 268: 423–426.

  12. Miki T et al. Am J Physiol 2002; 283: E1178–E1184.

  13. Amoroso S et al. Science 1990; 247: 852–854.

  14. Yamada K et al. Science 2001; 292: 1543–1546.

  15. Spanswick D et al. Nature 1997; 390: 521–525.

Download references

Acknowledgements

The authors are supported by the National Institutes of Health, American Heart Association, Marriott Foundation, Miami Heart Research Institute, Bruce and Ruth Rappaport Program, and the American Physicians Fellowship for Medicine in Israel. AT is an Established Investigator of the American Heart Association.

Author information

Authors and Affiliations

  1. Departments of Medicine and Molecular Pharmacology and Experimental Therapeutics, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, 55905, MN, USA

    L V Zingman, D M Hodgson, A E Alekseev & A Terzic

Authors
  1. L V Zingman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D M Hodgson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A E Alekseev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Terzic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Terzic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zingman, L., Hodgson, D., Alekseev, A. et al. Stress without distress: homeostatic role for KATP channels. Mol Psychiatry 8, 253–254 (2003). https://doi.org/10.1038/sj.mp.4001323

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001323

This article is cited by

Search

Advanced search

Quick links