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Pharmacological investigation of the role of ion channels in salivary secretion

  • Exocrine Glands
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Abstract

The role of K+ and Cl− channels in salivary secretion was investigated, with emphasis on the potential role of Ca2+-activated K+ channels. Ligand saturation kinetic assays and autoradiography showed large-conductance (BK) K+ channels to be highly expressed in rat submandibular and parotid glands, whereas low-conductance (SK) K+ channels could not be detected. To investigate the role of K+ and Cl− channels in secretion, intact rabbit submandibular glands were vascularly perfused and secretion induced by 10 µM ACh. Secretion was inhibited by 34±3% following perfusion with the general K+ channel inhibitor Ba2+ (5 mM), whereas organic inhibitors of BK (200 nM paxilline) or intermediate-conductance (IK) K+ channels (5 µM clotrimazole) had no effect. Secretion was strongly influenced by Cl− channel inhibitors, as 100 µM 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) completely abolished, while 10 µM NPPB, 20 µM NS1652 and 20 µM NS3623 reduced secretion by 34±3%, 23±3% and 59±4%, respectively. In conclusion, although high expression levels of BK channels were demonstrated, pharmacological tools failed to demonstrate any role for BK, IK or SK channels in salivary secretion in the rabbit submandibular gland. Other types of K+ channel, however, and particularly Cl− channels, are essential for ACh-induced salivary secretion.

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Acknowledgements

Dr. Bo. S. Jensen and Dr. Tino Jørgensen (NeuroSearch A/S, Denmark) are thanked for helpful discussions. Dr. Hans-Günther Knaus (University of Innsbruck, Austria) is thanked for donating the 125I-IbTX-D19Y/Y36F. Dr. Philip K. Ahring (NeuroSearch A/S, Denmark) is thanked for providing the stable HEK293 cell line expressing BK channels. Grazyna M. Poulsen is thanked for excellent technical assistance. NeuroSearch A/S, Denmark, is thanked for donating NS1652 and NS3623. The Novo Nordisk Foundation, The Carlsberg Foundation, The John and Birthe Meyer Foundation, The Danish Heart Foundation and The Danish Natural and Medical Sciences Research Councils provided funding.

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Authors and Affiliations

  1. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark

    Tina C. Stummann, Jørgen H. Poulsen, Morten Grunnet, Dan A. Klaerke, Hanne B. Rasmussen, Søren-Peter Olesen & Nanna K. Jorgensen

  2. Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark

    Anders Hay-Schmidt

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  1. Tina C. Stummann
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Correspondence to Nanna K. Jorgensen.

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Stummann, T.C., Poulsen, J.H., Hay-Schmidt, A. et al. Pharmacological investigation of the role of ion channels in salivary secretion. Pflugers Arch - Eur J Physiol 446, 78–87 (2003). https://doi.org/10.1007/s00424-002-0985-8

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