颈动脉体对化学信号的换能作用.pdfVIP

128 Acta Physiologica Sinica , April 25, 2007, 59 (2): 128-132 Brief Review Translating blood-borne stimuli: chemotransduction in the carotid body * Prem KUMAR B. Sc. , D. Phil Department of Physiology, The Medical School, University of Birmingham, Birmingham B15 2TT, UK Abstract: The carotid body can transduce hypoxia and other blood-borne stimuli, perhaps including hypoglycaemia, into afferent neural discharge that is graded for intensity and which forms the afferent limb of a cardiorespiratory and neuroendocrine reflex loop. Hypoxia inhibits a variety of K+ channels in the type I cells of the carotid body, in a seemingly species-dependent manner, and the resultant membrane depolarisation is sufficient to activate voltage-gated Ca2+ entry leading to neurosecretion and afferent discharge. The ion channels that respond to hypoxia appear to do so indirectly and recent work has therefore focussed upon identification of other proteins in the type I cells of the carotid body that may play key roles in the oxygen sensing process. Whilst a role for mitochondrial and/or NADPH-derived reactive oxygen species (ROS) has been proposed, the evidence for their signalling hypoxia in the carotid body is presently less than compelling and two alternate hypotheses are currently being tested further. The first implicates haemoxygenase 2 (HO-2), which may control specific K+ channel activation through O -dependent production of the signalling molecule, carbon 2 monoxide. The second hypothesis suggests a role for the cellular energy sensor, AMP-activated protein kinase (AMPK), which can inhibit type I cell K+ channels and increase afferent discharge when activated by hypoxia-induced elevations in the AMP: