Carotid Body Type-I Cells Under Chronic Sustained Hypoxia: Focus on Metabolism and Membrane Excitability.

Raúl Pulgar-Sepúlveda,Rodrigo Del Rio,Rodrigo Iturriaga,Fernando C Ortiz,Rodrigo Varas

doi:10.3389/fphys.2018.01282

Abstract

Chronic sustained hypoxia (CSH) evokes ventilatory acclimatization characterized by a progressive hyperventilation due to a potentiation of the carotid body (CB) chemosensory response to hypoxia. The transduction of the hypoxic stimulus in the CB begins with the inhibition of K+ currents in the chemosensory (type-I) cells, which in turn leads to membrane depolarization, Ca2+ entry and the subsequent release of one- or more-excitatory neurotransmitters. Several studies have shown that CSH modifies both the level of transmitters and chemoreceptor cell metabolism within the CB. Most of these studies have been focused on the role played by such putative transmitters and modulators of CB chemoreception, but less is known about the effect of CSH on metabolism and membrane excitability of type-I cells. In this mini-review, we will examine the effects of CSH on the ion channels activity and excitability of type-I cell, with a particular focus on the effects of CSH on the TASK-like background K+ channel. We propose that changes on TASK-like channel activity induced by CSH may contribute to explain the potentiation of CB chemosensory activity.

Highlights

The carotid body (CB) is the main peripheral chemoreceptor in mammals
Potentiation of CB chemosensory responses is an absolute requirement for ventilatory acclimatization
In the present review we focused on evidences suggesting that type-I cells excitability and metabolism undergoes substantial changes when exposed to chronic sustained hypoxia (CSH)

Summary

Introduction

The carotid body (CB) is the main peripheral chemoreceptor in mammals. Natural stimuli such as hypoxemia, hypercapnia, and/or acidosis increase the firing rate of the petrosal ganglion (PG) sensory afferent neurons projecting to the cardiovascular and respiratory regions in the brain stem (Gonzalez et al, 1994).The current model for hypoxic chemoreception states that hypoxia evokes a depolarization of CB type-I (glomus) cells, leading to an increment of intracellular Ca2+ and the subsequent release of one- or more-excitatory neurotransmitters to the nerve terminals of the PG neurons (Gonzalez et al, 1994; Iturriaga and Alcayaga, 2004; Nurse, 2005). In addition to the enhanced CB chemosensory responses, chronic sustained hypoxia (CSH) for weeks or months induces angiogenesis in the CB along with type-I cell hypertrophy and hyperplasia (Heath et al, 1985). Some reports indicate that CSH increases type-I cell excitability due to changes in K+ and Na+ channels expression.

Results

Conclusion