Skip to main content
SpringerLink
Log in

Negative cooperativity may explain flat concentration-response curves of ATP-sensitive potassium channels

  • Published:
European Biophysics Journal Aims and scope Submit manuscript

Abstract

Blockage of ATP-sensitive K+ channels by various drugs has been reported to exhibit a weak concentration dependence with Hill coefficients below unity. This phenomenon is interpreted by a negative cooperativity between K+ channels whereby drug binding to one channel lowers the drug affinities of neighbouring channels. Results are presented for a dimeric and a tetrameric channel model and compared with published experimental data.

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

  • Bodewei R, Hehl S, Neumcke B (1992) The cardiotonic bipyridine AWD 122–60 inhibits adenosine triphosphate-sensitive potassium channels of mouse skeletal muscle. Naunyn-Schmiedeberg's Arch Pharmacol 345:570–577

    Google Scholar 

  • Dunne MJ, Petersen OH (1986) Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin-secreting cell line. FEBS Lett 208:59–62

    Google Scholar 

  • Fersht A (1985) Enzyme Structure and Mechanism, 2nd edn. WH Freeman and Company, New York

    Google Scholar 

  • Honoré E, Attali B, Romey G, Lesage F, Barhanin J, Lazdunski M (1992) Different types of K+ channel current are generated by different levels of a single mRNA. The EMBO J 11:2465–2471

    Google Scholar 

  • Hopkins WF, Fatherazi S, Cook DL (1990) The oral hypoglycemic agent, U-56324, inhibits the activity of ATP-sensitive potassium channels in cell-free membrane patches from cultured mouse pancreatic B-cells. FEBS Lett 277:101–104

    Google Scholar 

  • Hymel L, Striessnig J, Glossmann H, Schindler H (1988) Purified skeletal muscle 1,4-dihydropyridine receptor forms phosphorylation-dependent oligomeric calcium channels in planar bilayers. Proc Natl Acad Sci, USA 85:4290–4294

    Google Scholar 

  • Kakei M, Kelly RP, Ashcroft SJH, Ashcroft FM (1986) The ATP-sensitivity of K+ channels in rat pancreatic B-cells is modulated by ADP. FEBS Lett 208:63–66

    Google Scholar 

  • Kolb H-A, Bamberg E (1977) Influence of membrane thickness and ion concentration on the properties of the gramicidin A channel: Autocorrelation, spectral power density, relaxation and single-channel studies. Biochim Biophys Acta 464:127–141

    Google Scholar 

  • Koshland Jr DE, Némethy G, Filmer D (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5:365–385

    Google Scholar 

  • Neumcke B, Stämpfli R (1983) Alteration of the conductance of Na+ channels in the nodal membrane of frog nerve by holding potential and tetrodotoxin. Biochim Biophys Acta 727:177–184

    Google Scholar 

  • Queyroy A, Verdetti J (1992) Cooperative gating of chloride channel subunits in endothelial cells. Biochim Biophys Acta 1108:159–168

    Google Scholar 

  • Schindler H, Spillecke F, Neumann E (1984) Different channel properties of Torpedo acetylcholine receptor monomers and dimers reconstituted in planar membranes. Proc Natl Acad Sci, USA 81:6222–6226

    Google Scholar 

  • Schwanstecher C, Dickel C, Panten U (1992) Cytosolic nucleotides enhance the tolbutamide sensitivity of the ATP-dependent K+ channel in mouse pancreatic B cells by their combined actions at inhibitory and stimulatory receptors. Mol Pharmacol 41:480–486

    Google Scholar 

  • Tung RT, Kurachi Y (1991) On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig. J Physiol (Lond) 437:239–256

    Google Scholar 

  • Tytgat J, Hess P (1992) Evidence for cooperative interactions in potassium channel gating. Nature 359:420–423

    Google Scholar 

  • Weik R, Lönnendonker U, Neumcke B (1989) Low-conductance states of K+ channels in adult mouse skeletal muscle. Biochim Biophys Acta 983:127–134

    Google Scholar 

  • Woll KH, Neumcke B (1987) Conductance properties and voltage dependence of an anion channel in amphibian skeletal muscle. Pflügers Arch 410:641–647

    Google Scholar 

  • Zünkler BJ, Lins S, Ohno-Shosaku T, Trube G, Panten U (1988) Cytosolic ADP enhances the sensitivity to tolbutamide of ATP-dependent K+ channels from pancreatic B-cells. FEBS Lett 239:241–244

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. I. Physiologisches Institut, Universität des Saarlandes, W-6650, Homburg/Saar, Germany

    S. Hehl & B. Neumcke

Authors
  1. S. Hehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Neumcke
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Correspondence to: S. Hehl

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hehl, S., Neumcke, B. Negative cooperativity may explain flat concentration-response curves of ATP-sensitive potassium channels. Eur Biophys J 22, 1–4 (1993). https://doi.org/10.1007/BF00205806

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00205806

Key words

Search

Navigation