CO2 chemosensory transduction and the control of respirationSupported by the MRC
Breathing is a vital physiological function that is continually adapted to metabolic activity. Peripheral and central chemosensors, which monitor the levels of O2 and CO2 in arterial blood and brain respectively, are essential components of the homeostatic controls that adjust respiratory activity to keep these blood gasses at their physiological levels.
If PCO2 in arterial blood increases (hypercapnia), ventilatory frequency rapidly increases. This reflex is mainly mediated by central chemoreceptors located at the highly vascularised ventral surface of the medulla oblongata. These chemosensors respond to changes in brain CO2/pH. The importance of the central chemoreceptors can be demonstrated by the persistence of the ventilatory response to hypercapnia after deafferentation of the peripheral chemoreceptors. Although this has been known for a long time, as has indeed the general location of CO2 chemosensors within the medulla, the mechanisms of CO2 chemoreception remain one of the mysteries of the respiratory field. It is often assumed in the field that CO2 is detected via a change in pH, however our latest results show that it can additionally be detected directly as CO2 (see below)
Disorders of the chemosensory control of breathing can have serious consequences. For example, Sudden Infant Death Syndrome (SIDS) involves cessation of breathing during sleep. An intriguing mystery of SIDS is that blood PCO2 must greatly increase, and blood PO2 must dramatically fall, during the fatal apnoea. Both events are a powerful drive for respiration and would normally ensure restarting of ventilation. For some reason this does not happen, consequently SIDS has been proposed to result from defective chemosensory mechanisms. Ondine's curse is a condition where the chemosensory control of breathing is deficient during sleep, but is relatively normal during wakefulness -clearly these patients are at risk of apnoea when asleep.
An article in Physiology News, Autumn 2011, vol 84 pp. 32-34 summarises some of our recent work in an accessible format.
Banner illustration: montage of CO2-dependent dye loading (FITC) and GFAP staining at the ventral surface of the medulla oblongata. This demonstrates the importance for the response to CO2 of large conductance channels in glial cells at the surface of the medulla.