Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

Asuncion Rocher,Ana Isabel Caceres,Constancio Gonzalez,Ana Obeso

doi:10.3390/md9122683

Asuncion Rocher, Ana Isabel Caceres + Show 2 more

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https://doi.org/10.3390/md9122683

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Abstract

Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO2 (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO2 removal from alveoli and a decrease in alveolar PCO2 ensues. Reduced alveolar PCO2 makes possible alveolar and arterial PO2 to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O2 detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O2-sensing.

Highlights

A Summary of Carotid Body (CB) General Function and Mechanisms up to the Mid-1980sThe carotid bodies (CBs) were discovered towards the middle of eighteen century, and thought for many years to be a small ganglion of the vegetative or autonomic nervous system
It appeared that the electrophysiological approach to the problem of sensory transduction in the chemoreceptor cells of the CB must rely on the recently developed patch-clamp technique [66]
Several people from our laboratory spent almost the entire year of 1987 going to the slaughter house to get calf CBs that would produce a yield of chemoreceptor cells that we were able to isolate at near purity, in which we can measure ionic concentrations by flame photometry and the release of CA using radioisotopic method [67]

Summary

Introduction

A Summary of Carotid Body (CB) General Function and Mechanisms up to the Mid-1980sThe carotid bodies (CBs) were discovered towards the middle of eighteen century, and thought for many years to be a small ganglion of the vegetative or autonomic nervous system. The appearance in January 1988 of the paper by Avenet et al [69] showing that sweet stimulus mediated increase in cAMP in taste receptor causes receptor depolarization via inhibition of K+ channels drove the attention to K+ currents and there it was: freshly isolated chemoreceptor cells of the rabbit CB have a component of their K+ currents that was reversibly inhibited by hypoxia [70].

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Conclusion