CO2/H+ homeostasis: Role of central and peripheral chemoreceptors in adult mammals

Abstract

CO2 and H+ are metabolic end-products, which are produced continuously and excreted steadily to maintain steady-state concentrations of CO2/H+ in the body, primarily by the chemoreceptors. To help maintain an adequate speed of reaction compatible with life, these reactions are enhanced by carbonic anhydrase (CA) present in the chemoreceptor cells. The role of chemoreceptors in H+ homeostasis is the focus of this chapter. The peripheral chemoreceptors very readily sense CO2/H+ and stimulate ventilation in order to enhance CO2 exhalation. Central chemoreceptors are stimulated similarly but slowly, also resulting in increased ventilation. Altogether, this phase, assisted by respiration alone, can be defined as the acute response. However, the H+ left behind is excreted by the renal system, rather slowly (chronic phase) without any direct intervention by the chemoreceptors. Thus, respiratory and renal systems are integrated in the long run to maintain CO 2/H+ homeostasis. A consensus model of CO 2/H+ stimulatory response is as follows: CO 2/H+ stimulus → Cellular K+ current suppression → Cell depolarization → Voltage-dependent Ca2+ gate opens → Ca2+ influx andstore-operated Ca2+ release → [Ca2+] i rise → Neurotransmission → Instantaneous chemosensory discharge (acute effects like hypoxia). At the same time, ATP comes into play as a neurotransmitter, but experimental data suggest a complex mechanism of interactions. Spyer et al. (2004) proposed ATP as the key neurotransmitter, but that the CO2 response is not affected by PPADS (ATP antagonist) in in vitro preparation. Additionally, recent data from P2X2 knockout mice showed a normal response to CO2, suggesting that purinergic mechanisms are not involved in central chemoreception. However, this leaves out a role of CO2/H + sensing in the peripheral chemoreceptors. Turning to constancy of [H+] in the fluid matrix of the body at the body temperature, it remains a fundamental condition of life, a legacy of Claude Bernard. © 2007 Springer Science+Business Media, LLC. All rights reserved.