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Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review

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Medical and Biomedical Updates

Part of the book series: Advances in Experimental Medicine and Biology ((CLEXBI,volume 1289))

Abstract

This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IP3R/s) regulating the intracellular calcium content [Ca2+]c in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex. [Ca2+]c changes were measured using cellular Ca2+-sensitive fluorescent probes, and carotid sinus nerve (CSN) sensory discharge was recorded with bipolar electrodes in in vitro perfused-superfused rat carotid body preparations. The cell-permeant, 2-amino-ethoxy-diphenyl-borate (2-APB; 100 μM) and curcumin (50 μM) were used as the inhibitors of IP3R/s. These agents suppressed the [Ca2+]c, and CSN discharge increases in hypoxia but not in hypercapnia, leading to the conclusion that only the hypoxic effects were mediated via modulation of IP3R/s. The ATP-induced Ca2+ release from intracellular stores in a Ca2+-free medium was blocked with 2-APB, supporting this conclusion.

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Acknowledgments

Supported by grants R-37-HL-43413-14, ROI-HL-50180-10, T-32-07027-29, and ONR-N-00014-01-0948. This article is a tribute to the late Professor Sukhamay Lahiri, one of the most distinguished figures of carotid body research in the second half of the twentieth century. The authors, coming from various corners of the world, had the fortune to be alumni at Prof. Lahiri’s Lab at the Department of Physiology of the University of Pennsylvania in Philadelphia over the years past and to share his research passion and undaunted efforts to get to the kernels of carotid body chemosensing mechanisms.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accord with the ethical standards of the institutions and practice at which the studies were conducted.

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Authors and Affiliations

  1. Department of Physiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    Anil Mokashi & Sukhamay Lahiri

  2. Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada

    Arijit Roy

  3. Department of Drug Discovery, Galleon Pharmaceuticals, Inc., Horsham, PA, USA

    Santhosh M. Baby

  4. Pennsylvania State University, Altoona, PA, USA

    Eileen M. Mulligan

  5. Department of Neurosciences Imaging and Clinical Sciences, University of Chieti-Pescara, Chieti, Italy

    Camillo Di Giulio

  6. Institute of Health Sciences, University of Opole, Opole, Poland

    Mieczyslaw Pokorski

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    Mieczyslaw Pokorski

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Mokashi, A. et al. (2020). Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review. In: Pokorski, M. (eds) Medical and Biomedical Updates. Advances in Experimental Medicine and Biology(), vol 1289. Springer, Cham. https://doi.org/10.1007/5584_2020_561

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