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Differential Regulation of ASICs and TRPV1 by Zinc in Rat Bronchopulmonary Sensory Neurons

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Abstract

Purpose

Zinc has been known to act as a signaling molecule that regulates a variety of neuronal functions. In this study, we aimed to study the effect of zinc on two populations of acid-sensitive ion channels, acid-sensing ion channels (ASICs), and transient receptor potential vanilloid receptor-1 (TRPV1), in vagal bronchopulmonary sensory neurons.

Methods

Rat vagal sensory neurons innervating lungs and airways were retrogradely labeled with a fluorescent tracer. Whole-cell perforated patch-clamp recordings were carried out in primarily cultured bronchopulmonary sensory neurons. The acid-evoked ASIC and TRPV1 currents were measured and compared between before and after the zinc pretreatment.

Results

ASIC currents were induced by a pH drop from 7.4 to 6.8 or 6.5 in the presence of capsazepine (10 µM), a specific TRPV1 antagonist. Pretreatment with zinc (50 or 300 µM, 2 min) displayed different effects on the two distinct phenotypes of ASIC currents: a marked potentiation on ASIC channels with fast kinetics of activation and inactivation or no significant effect on ASIC currents with slow activation and inactivation. On the other hand, pretreatment with zinc significantly inhibited the acid (pH 5.5 or 5.3)-induced TRPV1 currents. The inhibition was abolished by intracellular chelation of zinc by TPEN (25 µM), indicating that intracellular accumulation of zinc was likely required for its inhibitory effect on TRPV1 channels.

Conclusions

Our study showed that zinc differentially regulates the activities of ASICs and TRPV1 channels in rat vagal bronchopulmonary sensory neurons.

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Acknowledgments

This study was supported in part by grants from American Heart Association, MEDCEN Community Health Foundation, and Mercer University School of Medicine.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA, 31207, USA

    Zhanna V. Vysotskaya, Charles R. Moss II & Qihai Gu

Authors
  1. Zhanna V. Vysotskaya
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  2. Charles R. Moss II
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  3. Qihai Gu
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Correspondence to Qihai Gu.

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Vysotskaya, Z.V., Moss, C.R. & Gu, Q. Differential Regulation of ASICs and TRPV1 by Zinc in Rat Bronchopulmonary Sensory Neurons. Lung 192, 927–934 (2014). https://doi.org/10.1007/s00408-014-9634-1

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  • DOI: https://doi.org/10.1007/s00408-014-9634-1

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