Paracrine Signaling in Glial-Like Type II Cells of the Rat Carotid Body.
Arterial Chemoreceptors in Physiology and Pathophysiology
Advances in experimental medicine and biology, January 2015
Murali, Sindhubarathi, Zhang, Min, Nurse, Colin A, Sindhubarathi Murali, Min Zhang, Colin A. Nurse
The carotid body (CB) chemosensory complex uses ATP as a key excitatory neurotransmitter that is the main contributor to the sensory discharge during acute hypoxia. The complex includes receptor type I cells, which depolarize and release various neurochemicals including ATP during hypoxia, and contiguous glial-like type II cells which express purinergic P2Y2 receptors (P2Y2R). We previously showed that activation of P2Y2R on rat type II cells led to the opening of pannexin-1 (Panx-1) channels, which acted as conduits for the further release of ATP. More recently, we considered the possibility that other CB neuromodulators may have a similar paracrine role, leading to the activation of type II cells. Here, we examine the evidence that angiotensin II (ANG II), endothelin- (ET-1), and muscarinic agonists (e.g. acetylcholine, ACh) may activate intracellular Ca(2+) signals in type II cells and, in the case of ANG II and ACh, Panx-1 currents as well. Using ratiometric Ca(2+) imaging, we found that a substantial population of type II cells responded to 100 nM ANG II with a robust rise in intracellular Ca(2+) and activation of Panx-1 current. Both effects of ANG II were mediated via AT1 receptors (AT1Rs) and current activation could be inhibited by the Panx-1 channel blocker, carbenoxolone (CBX; 5 μM). Additionally, low concentrations of ET-1 (1 nM) evoked robust intracellular Ca(2+) responses in subpopulations of type II cells. The mAChR agonist muscarine (10 μM) also induced a rise in intracellular Ca(2+) in some type II cells, and preliminary perforated-patch, whole-cell recordings revealed that ACh (10 μM) may activate Panx-1-like currents. These data suggest that paracrine activation of type II cells by endogenous neuromodulators may be a common feature of signal processing in the rat CB.
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