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 AT 1 receptors (AT 1 Rs) 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.
CITATION STYLE
Murali, S., Zhang, M., & Nurse, C. A. (2015). Paracrine signaling in glial-like type ii cells of the rat carotid body. Advances in Experimental Medicine and Biology, 860, 41–47. https://doi.org/10.1007/978-3-319-18440-1_5
Mendeley helps you to discover research relevant for your work.