Modulation of the carotid body sensory discharge by NO: an up-dated hypothesis.

The carotid body (CB) is a peripheral chemoreceptor organ that initiates compensatory reflex responses so as to maintain gas homeostasis. Stimuli such as low oxygen (hypoxia) and high CO(2)/H(+) (acid hypercapnia) cause an increase in 'afferent' sensory discharge that is relayed via the carotid sinus nerve (CSN) to the brainstem, resulting in corrective changes in ventilation. A parallel autonomic pathway has been recognized for >40 years as the source of 'efferent' inhibition of the CB sensory discharge and, more recently, nitric oxide (NO) has been identified as the key mediator. This review will examine our current understanding of the role of nNOS-positive autonomic neurons, embedded in 'paraganglia' within the glossopharyngeal (GPN) and CSN nerves, in mediating efferent CB chemoreceptor inhibition. We highlight recent data linking the actions of hypoxia, ACh and ATP to NO synthesis/release from GPN neurons. Finally, we consider the novel hypothesis that pannexin-1 channels present in GPN neurons may play a role in NO signaling during hypoxia.