Sensing hypoxia in the carotid body: from stimulus to response.
The carotid body is a peripheral sensory organ that can transduce modest falls in the arterial PO(2) (partial pressure of oxygen) into a neural signal that provides the afferent limb of a set of stereotypic cardiorespiratory reflexes that are graded according to the intensity of the stimulus. The stimulus sensed is tissue PO(2) and this can be estimated to be around 50 mmHg during arterial normoxia, falling to between 10-40 mmHg during hypoxia. The chemoafferent hypoxia stimulus-response curve is exponential, rising in discharge frequency with falling PO(2), and with no absolute threshold apparent in hyperoxia. Although the oxygen sensor has not been definitely identified, it is believed to reside within type I cells of the carotid body, and presently two major hypotheses have been put forward to account for the sensing mechanism. The first relies upon alterations in the cell energy status that is sensed by the cytosolic enzyme AMPK (AMP-activated protein kinase) subsequent to hypoxia-induced increases in the cellular AMP/ATP ratio during hypoxia. AMPK is localized close to the plasma membrane and its activation can inhibit both large conductance, calcium-activated potassium (BK) and background, TASK-like potassium channels, inducing membrane depolarization, voltage-gated calcium entry and neurosecretion of a range of transmitter and modulator substances, including catecholamines, ATP and acetylcholine. The alternative hypothesis considers a role for haemoxygenase-2, which uses oxygen as a substrate and may act to gate an associated BK channel through the action of its products, carbon monoxide and possibly haem. It is likely however, that these and other hypotheses of oxygen transduction are not mutually exclusive and that each plays a role, via its own particular sensitivity, in shaping the full response of this organ between hyperoxia and anoxia.
Kumar
Prem
P
Department of Physiology, The Medical School, University of Birmingham, Birmingham B15 2TT, U.K. p.kumar@bham.ac.uk
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000033:anatomy & histology / Q000473:pathology* / Q000502:physiology; D006801:Humans; D000860:Hypoxia; D008953:Models, Anatomic; D008954:Models, Biological; D008962:Models, Theoretical; D009474:Neurons / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D015221:Potassium Channels / Q000378:metabolism; D011312:Pressure
D015221:Potassium Channels; D010100:Oxygen; D002118:Calcium