In humans the intravenous anaesthetic propofol depresses ventilatory responses to hypoxia and CO2. Animal studies suggest that this may in part be due to inhibition of synaptic transmission between chemoreceptor glomus cells of the carotid body and the afferent carotid sinus nerve. It is however unknown if propofol can also act directly on the glomus cell. Here we report that propofol can indeed inhibit intracellular Ca2+ responses to hypoxia and hypercapnia in isolated rat glomus cells. Neither this propofol effect, nor the glomus cell response to hypoxia in the absence of propofol, were influenced by GABA receptor activation (using GABA, muscimol and baclofen) or inhibition (using bicuculline and 5-aminovaleric acid). Suggesting that these effects of propofol are not mediated through GABA receptors. Propofol inhibited calcium responses to nicotine in glomus cells but the nicotinic antagonists vecuronium and methyllycaconitine did not inhibit calcium responses to hypoxia. TASK channel activity was not altered by propofol. The glomus cell Ca2+ response to depolarisation with 30 mM K+ was however modestly inhibited by propofol. In summary we conclude that propofol does have a direct effect upon hypoxia signalling in isolated type-1 cells and that this may be partially due to its ability to inhibit voltage gated Ca2+v channels. We also note that propofol has the capacity to supress glomus cell excitation via nicotinic receptors and may therefore also interfere with paracrine/autocrine cholinergic signalling in the intact organ. The effects of propofol on chemoreceptor function are however clearly complex and require further investigation.
Respir Physiol Neurobiol
17 - 27
Carotid body, Chemosensitivity, Hypoxia, Propofol, Animals, Animals, Newborn, Calcium, Carbon Dioxide, Carotid Body, Cell Hypoxia, Chemoreceptor Cells, Cholinergic Agents, Dose-Response Relationship, Drug, Drug Interactions, GABA Agents, Hypercapnia, Hypnotics and Sedatives, Membrane Potentials, Patch-Clamp Techniques, Potassium, Propofol, Rats, Rats, Sprague-Dawley