Modulation of the carotid body sensory discharge by NO: An up-dated hypothesis.
ABSTRACT 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.
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ABSTRACT: Key points Carotid body (CB) chemoreceptor complexes consist of receptor type I cells, intimately associated with glia-like type II cells whose function is poorly understood. We show that type II cells in the rat CB express gap junction-like proteins, pannexin-1 (Panx-1) channels, which form non-selective pores permeable to ions and large molecules such as ATP, a key CB neurotransmitter. Activation of purinergic P2Y2 receptors on type II cells led to a rise in intracellular Ca(2+), and a prolonged membrane depolarization due to opening of Panx-1 channels. In a CB co-culture model, where purinergic P2X2/3-expressing petrosal neurones served as a reporter or biosensor of ATP release, we show that selective activation of P2Y2 receptors on type II cells can lead to ATP release via Panx-1 channels. We propose that type II cells may function as amplifiers of the neurotransmitter ATP during chemotransduction, via the mechanism of ATP-induced ATP release.The Journal of Physiology 06/2012; 590(Pt 17):4335-50. · 4.38 Impact Factor