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Reply to: Activation of BK channels may not be required for bitter tastant–induced bronchodilation

Nature Medicine volume 18, pages 650–651 (2012)Cite this article

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An et al. reply:

Zhang et al.1 responded to our paper2 in which we showed that bitter taste receptors (TAS2Rs) mediate relaxation of airway smooth muscle by increasing the concentration of intracellular calcium ([Ca2+]i). We are pleased to see that they also found TAS2R agonists to markedly relax airways, with similar efficacies to those that we found2. In our study we showed that TAS2R function in airways was mediated by [Ca2+]i release on the basis of the concordance of relaxation potency and efficacy with measured [Ca2+]i release, the loss of TAS2R-mediated relaxation when [Ca2+]i release was blocked and the stimulation of spatially and temporally distinct [Ca2+]i events evoked by TAS2R agonists in intact airway smooth muscle. We considered that large-conductance Ca2+-activated K+ channels (BKCa) were activated, and thus played some part in the relaxation response, on the basis of the sensitivity of TAS2R-mediated relaxation of mouse airways and individual airway smooth muscle cells to the highly specific BKCa-channel inhibitor iberiotoxin (IbTx). However, we showed that IbTx only partially blocked relaxation (Fig. 3b,c of the paper2) to bitter tastant, leaving open the possibility of additional mechanisms.

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Figure 1: Airway smooth muscle responses to the TAS2R agonist chloroquine are sensitive to the BKCa antagonist IbTx.

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Acknowledgements

Supported by the US National Institutes of Health grants HL071609 and HL107361.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

    Steven S An

  2. Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Kathryn S Robinett, Deepak A Deshpande, Wayne C H Wang & Stephen B Liggett

  3. Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Stephen B Liggett

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Correspondence to Stephen B Liggett.

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An, S., Robinett, K., Deshpande, D. et al. Reply to: Activation of BK channels may not be required for bitter tastant–induced bronchodilation. Nat Med 18, 650–651 (2012). https://doi.org/10.1038/nm.2734

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