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Arterial Chemoreceptors pp 61–68Cite as

Topical Application of Connexin43 Hemichannel Blocker Reduces Carotid Body-Mediated Chemoreflex Drive in Rats

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1071))

Abstract

The carotid body (CB) is the main arterial chemoreceptor involved in oxygen sensing. Upon hypoxic stimulation, CB chemoreceptor cells release neurotransmitters, which increase the frequency of action potentials in sensory nerve fibers of the carotid sinus nerve. The identity of the molecular entity responsible for oxygen sensing is still a matter of debate; however several ion channels have been shown to be involved in this process. Connexin-based ion channels are expressed in the CB; however a definitive role for these channels in mediating CB oxygen sensitivity has not been established. To address the role of these channels, we studied the effect of blockers of connexin-based ion channels on oxygen sensitivity of the CB. A connexin43 (Cx43) hemichannel blocking agent (CHBa) was applied topically to the CB and the CB-mediated hypoxic ventilatory response (FiO2 21, 15, 10 and 5%) was measured in adult male Sprague-Dawley rats (~250 g). In normoxic conditions, CHBa had no effect on tidal volume or respiratory rate, however Cx43 hemichannels inhibition by CHBa significantly impaired the CB-mediated chemoreflex response to hypoxia. CHBa reduced both the gain of the hypoxic ventilatory response (HVR) and the maximum HVR by ~25% and ~50%, respectively. Our results suggest that connexin43 hemichannels contribute to the CB chemoreflex response to hypoxia in rats. Our results suggest that CB connexin43 hemichannels may be pharmacological targets in disease conditions characterized by CB hyperactivity.

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Acknowledgments

This study was supported by Fondecyt 1140275 and 1180172 (RDR) and Fondecyt 1160227 (MAR). NJM is supported by a grant from the National Institutes of Health (HL-138600-01).

Author information

Authors and Affiliations

  1. Laboratory of Cardiorespiratory Control, Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile

    David C. Andrade, Camilo Toledo, Claudia M. Lucero, Hugo S. Díaz, Alexis Arce-Álvarez & Rodrigo Del Rio

  2. Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

    Rodrigo Iturriaga

  3. Centro de Fisiología Celular e Integrativa, Clínica Alemana Universidad Del Desarrollo, Santiago, Chile

    Mauricio A. Retamal

  4. Department of Physiology and Pharmacology, Des Moines University, Des Moines, IA, USA

    Noah J. Marcus

  5. Laboratorio de Fisiología Celular, Universidad de Chile, Santiago, Chile

    Julio Alcayaga

  6. Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago, Chile

    Rodrigo Del Rio

  7. Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

    Rodrigo Del Rio

Authors
  1. David C. Andrade
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  2. Rodrigo Iturriaga
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  3. Camilo Toledo
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  4. Claudia M. Lucero
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  5. Hugo S. Díaz
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  6. Alexis Arce-Álvarez
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  7. Mauricio A. Retamal
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  8. Noah J. Marcus
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  9. Julio Alcayaga
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  10. Rodrigo Del Rio
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Corresponding author

Correspondence to Rodrigo Del Rio .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    Estelle B. Gauda

  2. Faculty of Medical Sciences, Nova University of Lisbon Faculty of Medical Sciences, Lisbon, Portugal

    Maria Emilia Monteiro

  3. Department of Medicine, University of Chicago , Chicago, IL, USA

    Nanduri Prabhakar

  4. Department of Neuroscience, Cell Biology, Wright State University, Dayton, OH, USA

    Christopher Wyatt

  5. Cellular and Integrative Physiology, University of Nebraska, Omaha, NE, USA

    Harold D. Schultz

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Andrade, D.C. et al. (2018). Topical Application of Connexin43 Hemichannel Blocker Reduces Carotid Body-Mediated Chemoreflex Drive in Rats. In: Gauda, E., Monteiro, M., Prabhakar, N., Wyatt, C., Schultz, H. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 1071. Springer, Cham. https://doi.org/10.1007/978-3-319-91137-3_7

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