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On the functional interaction between nicotinic acetylcholine receptor and Na+,K+-ATPase

  • Skeletal Muscle
  • Published:
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Abstract

Previous studies have shown that nanomolar acetylcholine (ACh) produces a 2 to 4-mV hyperpolarization of skeletal muscle fibers putatively due to Na+,K+-ATPase activation. The present study elucidates the involvement of the nicotinic ACh receptor (nAChR) and of Na+,K+-ATPase isoform(s) in ACh-induced hyperpolarization of rat diaphragm muscle fibers. A variety of ligands of specific binding sites of nAChR and Na+,K+-ATPase were used. Dose–response curves for ouabain, a specific Na+,K+-ATPase inhibitor, were obtained to ascertain which Na+,K+-ATPase isoform(s) is involved. The ACh dose–response relationship for the hyperpolarization was also determined. The functional relationship between these two proteins was also studied in a less complex system, a membrane preparation from Torpedo electric organ. The possibility of a direct ACh effect on Na+,K+-ATPase was studied in purified lamb kidney Na+,K+-ATPase and in rat red blood cells, systems where no nAChR is present. The results indicate that binding of nAChR agonists to their specific sites results in modulation of ouabain-sensitive (most probably α2) isoform of Na+,K+-ATPase, leading to muscle membrane hyperpolarization. In the Torpedo preparation, ouabain modulates dansyl-C6-choline binding to nAChR, and vice versa. These results provide the first evidence of a functional interaction between nAChR and Na+,K+-ATPase. Possible interaction mechanisms are discussed.

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Acknowledgements

This work was supported by grants from the Russian Foundation for Basic Research (RFBR #04-04-49535); NIH MBRS#S06 GM50695; NIH RCMI#G12RR03035. We wish to thank Dr. Steen E Pedersen at the Baylor College of Medicine for his support with this project and for Torpedo californica tissue, dansyl-C6-choline, and use of the stopped-flow. We also appreciate Dr. Iraida Andreeva and Dr. Robert Meltzer at the Baylor College of Medicine, Dr. Maxim Dobretsov at the University of Arkansas for Medical Sciences, and Dr. Judy Heiny at the University of Cincinnati Medical Center for the discussions. In particular, we appreciated the support and advice of the late Dr. Julius Allen.

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Author notes

  1. Frederic Mandel

    Present address: Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267-0576, USA

Authors and Affiliations

  1. Department of General Physiology, St. Petersburg State University, 7/9 University emb., St. Petersburg, 199034, Russia

    Igor I. Krivoi, Violetta V. Kravtsova & Alexander N. Vasiliev

  2. A.A. Ukhtomski Institute of Physiology, St. Petersburg State University, 7/9 University emb., St. Petersburg, 199034, Russia

    Tatiana M. Drabkina

  3. Department of Biochemistry, University Central del Caribe, Bayamon, PR, 00960, USA

    Misty J. Eaton

  4. Department of Biochemistry and Department of Physiology, University Central del Caribe, Bayamon, PR, 00960, USA

    Serguei N. Skatchkov

  5. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA

    Frederic Mandel

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  1. Igor I. Krivoi
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Correspondence to Igor I. Krivoi.

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Krivoi, I.I., Drabkina, T.M., Kravtsova, V.V. et al. On the functional interaction between nicotinic acetylcholine receptor and Na+,K+-ATPase. Pflugers Arch - Eur J Physiol 452, 756–765 (2006). https://doi.org/10.1007/s00424-006-0081-6

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  • DOI: https://doi.org/10.1007/s00424-006-0081-6

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