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Molecular Pharmacology

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Rapid CommunicationAccelerated CommunicationA

Stoichiometry of Potassium Channel Opener Action

Insa Gross, Andreas Toman, Ingo Uhde, Christina Schwanstecher and Mathias Schwanstecher
Molecular Pharmacology December 1999, 56 (6) 1370-1373; DOI: https://doi.org/10.1124/mol.56.6.1370
Insa Gross
Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Germany
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Andreas Toman
Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Germany
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Ingo Uhde
Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Germany
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Christina Schwanstecher
Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Germany
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Mathias Schwanstecher
Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Germany
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Abstract

Potassium channel openers (KCOs; e.g., P1075, pinacidil) exert their effects on excitable cells by opening ATP-sensitive potassium channels. These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit plus a regulatory subunit comprising the receptor sites for hypoglycemic sulfonylureas and KCOs (a sulfonylurea receptor). To elucidate stoichiometry of KCO action, we analyzed P1075 sensitivity of channels coassembled from sulfonylurea receptor isoforms with high or low P1075 affinity. Concentration activation curves for cDNA ratios of 1:1 or 1:10 resembled those for channel opening resulting from interaction with a single site, whereas models for activation requiring occupation of two, three, or four sites were incongruous. We conclude KCO-induced channel activation to be mediated by interaction with a single binding site per tetradimeric complex.

Footnotes

    • Received July 14, 1999.
    • Accepted September 1, 1999.
  • Send reprint requests to: Dr. M. Schwanstecher, Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Mendelssohnstraβe 1, 38106 Braunschweig, Germany. E-mail: M.Schwanstecher{at}tu-bs.de

  • This work was supported by grants from the Deutsche Forschungsgemeinschaft (to M.S. and C.S.).

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 56 (6)
Molecular Pharmacology
Vol. 56, Issue 6
1 Dec 1999
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Rapid CommunicationAccelerated CommunicationA

Stoichiometry of Potassium Channel Opener Action

Insa Gross, Andreas Toman, Ingo Uhde, Christina Schwanstecher and Mathias Schwanstecher
Molecular Pharmacology December 1, 1999, 56 (6) 1370-1373; DOI: https://doi.org/10.1124/mol.56.6.1370

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Rapid CommunicationAccelerated CommunicationA

Stoichiometry of Potassium Channel Opener Action

Insa Gross, Andreas Toman, Ingo Uhde, Christina Schwanstecher and Mathias Schwanstecher
Molecular Pharmacology December 1, 1999, 56 (6) 1370-1373; DOI: https://doi.org/10.1124/mol.56.6.1370
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