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.

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

Di Giulio
2021

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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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/732374
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