Signal processing at mammalian carotid body chemoreceptors

Mammalian carotid bodies are richly vascularized chemosensory organs that sense blood levels of O2, CO2/H+, and glucose and maintain homeostatic regulation of these levels via the reflex control of ventilation. Carotid bodies consist of innervated clusters of type I (or glomus) cells in intimate association with glial-like type II cells. Carotid bodies make afferent connections with fibers from sensory neurons in the petrosal ganglia and receive efferent inhibitory innervation from parasympathetic neurons located in the carotid sinus and glossopharyngeal nerves. There are synapses between type I (chemosensory) cells and petrosal afferent terminals, as well as between neighboring type I cells. There is a broad array of neurotransmitters and neuromodulators and their ionotropic and metabotropic receptors in the carotid body. This allows for complex processing of sensory stimuli (e.g., hypoxia and acid hypercapnia) involving both autocrine and paracrine signaling pathways. This review summarizes and evaluates current knowledge of these pathways and presents an integrated working model on information processing in carotid bodies. Included in this model is a novel hypothesis for a potential role of type II cells as an amplifier for the release of a key excitatory carotid body neurotransmitter, ATP, via P2Y purinoceptors and pannexin-1 channels.

► ATP as an excitatory sensory transmitter in the carotid body.
► Role of ACh, adenosine, 5-HT, GABA, dopamine, ATP, histamine as neuromodulators.
► Autocrine–paracrine signaling in the carotid body.
► ATP-mediated gliotransmission in the carotid body.
► Proposed role of pannexin-1 channels in “ATP-induced ATP release” by type II cells.