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

Nature Medicine volume 18, pages 648–650 (2012)Cite this article

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To the Editor:

Deshpande et al.1 reported that bitter tastants increase intracellular Ca2+ concentration (to similar levels produced by the bronchoconstrictive agonists histamine and bradykinin) yet cause marked bronchodilation. This implies that elevated Ca2+ concentration inhibits contraction, challenging the classic Ca2+-dependent mechanism underlying smooth muscle contraction2,3. To resolve this apparent paradox, the authors showed that bitter tastants can generate localized Ca2+ events, and that bitter tastant-induced relaxation and hyperpolarization can be inhibited by the large-conductance Ca2+-activated K+ (BK) channel antagonist iberiotoxin1; thus, they propose that bitter tastant–induced bronchodilation results from its ability to generate localized Ca2+ signals, which in turn open BK channels and hyperpolarize the membrane. However, their assertion of the involvement of BK channel activation was solely based on the effect of iberiotoxin on bitter tastant–induced relaxation and change in membrane potential as assessed by voltage-sensitive dyes. We are concerned that the association of BK channel activity with relaxation has not been directly examined, raising questions about the proposed relaxation mechanism. We therefore directly studied the effect of bitter tastants on the activity of BK channels and examined the relaxation effect of multiple BK channel inhibitors in mouse airway smooth muscle, the same type of smooth muscle tissue used in Deshpande et al.1.

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Figure 1: Effect of chloroquine on BK channel currents in mouse airway smooth muscle cells.
Figure 2: Lack of an effect of BK channel blockers on bitter tastant–induced relaxation in mouse intrapulmonary mainstem bronchi.

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Acknowledgements

We thank J. Walsh for helpful discussions. This work was supported by US National Heart, Lung, and Blood Institute grant HL73875 (to R.Z.) and the National Basic Research Program of China (2009CB941602) (to M.-S.Z.).

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Author notes

  1. Min-Sheng Zhu and Ronghua ZhuGe: These authors contributed equally to this work.

Authors and Affiliations

  1. Model Animal Research Center, Nanjing University, Nanjing, China

    Cheng-Hai Zhang, Chen Chen & Min-Sheng Zhu

  2. School of Life Sciences, Wenzhou Medical College, Wenzhou, China

    Chen Chen & Min-Sheng Zhu

  3. Biomedical Imaging Group, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Lawrence M Lifshitz, Kevin E Fogarty & Ronghua ZhuGe

  4. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Lawrence M Lifshitz & Kevin E Fogarty

  5. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Ronghua ZhuGe

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  1. Cheng-Hai Zhang
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Correspondence to Min-Sheng Zhu or Ronghua ZhuGe.

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Zhang, CH., Chen, C., Lifshitz, L. et al. Activation of BK channels may not be required for bitter tastant–induced bronchodilation. Nat Med 18, 648–650 (2012). https://doi.org/10.1038/nm.2733

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