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

Marine Drugs

Asuncion Rocher¹  Ana Isabel Caceres²  Ana Obeso² 

[1]Department of Biochemistry and Molecular Biology and Physiology, School of Medicine-IBGM, CIBER of Respiratory Diseases, ISCiii, University of Valladolid, 47005-Valladolid, Spain

关键词: carotid body;    O₂-sensing;    tetrodotoxin;    TTX;    veratridine;    dihydropyridine;    catecholamine;   

DOI  :  10.3390/md9122683

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.