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Letters to Nature

Nature 413, 631-635 (11 October 2001) | doi:10.1038/35098087; Received 31 January 2001; Accepted 22 August 2001

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Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli

David R. Stevens1, Reinhard Seifert2, Bernd Bufe3, Frank Müller2, Elisabeth Kremmer4, Renate Gauss2, Wolfgang Meyerhof3, U. Benjamin Kaupp2 & Bernd Lindemann1

  1. Department of Physiology, Universität des Saarlandes, D-66421 Homburg, Germany
  2. Institute for Biological Information Processing, Forschungszentrum Jülich, D-52425 Jülich, Germany
  3. Department of Molecular Genetics, Deutsches Institut für Ernährungsforschung, Arthur-Scheunert-Allee 114-116, D-14558 Potsdam-Rehbrücke, Germany
  4. Institute for Molecular Immunology, GSF, D-81377 München, Germany

Correspondence to: Bernd Lindemann1 Correspondence and requests for materials should be addressed to B.L. (e-mail: Email: phblin@uniklinik-saarland.de).

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Sour taste is initiated by protons acting at receptor proteins or channels. In vertebrates, transduction of this taste quality involves several parallel pathways1, 2, 3, 4, 5. Here we examine the effects of sour stimuli on taste cells in slices of vallate papilla from rat. From a subset of cells, we identified a hyperpolarization-activated current that was enhanced by sour stimulation at the taste pore. This current resembled Ih found in neurons and cardio-myocytes6, 7, a current carried by members of the family of hyperpolarization-activated and cyclic-nucleotide-gated (HCN) channels8, 9, 10, 11, 12, 13. We show by in situ hybridization and immunohistochemistry that HCN1 and HCN4 are expressed in a subset of taste cells. By contrast, gustducin, the G-protein involved in bitter and sweet taste14, is not expressed in these cells. Lowering extracellular pH causes a dose-dependent flattening of the activation curve of HCN channels and a shift in the voltage of half-maximal activation to more positive voltages. Our results indicate that HCN channels are gated by extracellular protons and may act as receptors for sour taste.