title: Paracrine Signaling in Glial-Like Type II Cells of the Rat Carotid Body.
abstract: 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.
authors: Department of Biology, McMaster University, Hamilton, ON, L8S 4K1, Canada.
authors: Sindhubarathi
authors: S
authors: Murali
authors: Min
authors: M
authors: Zhang
authors: Colin A
authors: CA
authors: Nurse
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D009457:Neuroglia / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology
chemical_list: D019332:Endothelin-1; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D002118:Calcium