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

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Abstract

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.

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Figure 1: Recordings from rat taste cells.
Figure 2: Identification of HCN mRNAs in rat vallate papilla.
Figure 3: Immunohistochemical localization of HCN1 and HCN4 isoforms.
Figure 4: Activation of heterologously expressed HCN1 and HCN4 channels by extracellular protons.

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Acknowledgements

We thank the Deutsche Forschungsgemeinschaft for support.

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Authors and Affiliations

  1. Department of Physiology, Universität des Saarlandes, Homburg, D-66421, Germany

    David R. Stevens & Bernd Lindemann

  2. Institute for Biological Information Processing, Forschungszentrum Jülich, Jülich, D-52425, Germany

    Reinhard Seifert, Frank Müller, Renate Gauss & U. Benjamin Kaupp

  3. Department of Molecular Genetics, Deutsches Institut für Ernährungsforschung, Arthur-Scheunert-Allee 114-116, Potsdam-Rehbrücke, D-14558, Germany

    Bernd Bufe & Wolfgang Meyerhof

  4. Institute for Molecular Immunology, GSF, München, D-81377, Germany

    Elisabeth Kremmer

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  1. David R. Stevens
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  2. Reinhard Seifert
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  3. Bernd Bufe
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  4. Frank Müller
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  6. Renate Gauss
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  8. U. Benjamin Kaupp
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  9. Bernd Lindemann
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Correspondence to Bernd Lindemann.

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Stevens, D., Seifert, R., Bufe, B. et al. Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature 413, 631–635 (2001). https://doi.org/10.1038/35098087

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  • DOI: https://doi.org/10.1038/35098087

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