Translating blood-borne stimuli: chemotransduction in the carotid body

Prem Kumar

Research output: Contribution to journalArticle

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 Ca(2+) 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 O2-dependent production of the signalling molecule, carbon 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: ATP ratio. The apparent richness of O2-sensitive K(+) channels and sensor mechanisms within this organ may indicate a redundancy system for this vital cellular process or it may be that each protein contributes differently to the overall response, for example, with different O2 affinities. The mechanism by which low glucose is sensed is not yet known, but recent evidence suggests that it is not via closure of K(+) channels, unlike the hypoxia transduction process.
Original languageEnglish
Pages (from-to)128-32
Number of pages5
JournalActa Physiologica Sinica
VolumeIn Press
Publication statusPublished - 1 Jan 2007

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