A novel O2-sensing mechanism in rat glossopharyngeal neurones mediated by a halothane-inhibitable background K+ conductance

• Published in: The Journal of physiology Vol. 548; no. 3; pp. 731 - 743
• Main Authors: Campanucci, Verónica A, Fearon, Ian M, Nurse, Colin A
• Format: Journal Article
• Language: English
• Published: England The Physiological Society 01-05-2003; Blackwell Science Inc
• Subjects: Animals; Arachidonic Acids - pharmacology; Cell Hypoxia; Cells, Cultured; Dihydrolipoamide Dehydrogenase - metabolism; Endocannabinoids; Glossopharyngeal Nerve - physiology; Halothane - pharmacology; In Vitro Techniques; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neurons - drug effects; Neurons - physiology; Original; Oxygen Consumption; Patch-Clamp Techniques; Polyunsaturated Alkamides; Potassium Channels - drug effects; Potassium Channels - physiology; Rats; Rats, Wistar; Ruthenium Red - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2002.035998

Modulation of K + channels by hypoxia is a common O 2 -sensing mechanism in specialised cells. More recently, acid-sensitive TASK-like background K + channels, which play a key role in setting the resting membrane potential, have been implicated in O 2 -sensing in certain cell types. Here, we report a novel O 2 sensitivity mediated by a weakly pH-sensitive background K + conductance in nitric oxide synthase (NOS)-positive neurones of the glossopharyngeal nerve (GPN). This conductance was insensitive
to 30 m m TEA, 5 m m 4-aminopyridine (4-AP) and 200 μ m Cd 2+ , but was reversibly inhibited by hypoxia (O 2 tension ( P O 2 ) = 15 mmHg), 2–5 m m halothane, 10 m m barium and 1 m m quinidine. Notably, the presence of halothane occluded the inhibitory effect of hypoxia. Under current clamp, these agents
depolarised GPN neurones. In contrast, arachidonic acid (5–10 μ m ) caused membrane hyperpolarisation and potentiation of the background K + current. This pharmacological profile suggests the O 2 -sensitive conductance in GPN neurones is mediated by a class of background K + channels different from the TASK family; it appears more closely related to the THIK (tandem pore domain halothane-inhibited
K + ) subfamily, or may represent a new member of the background K + family. Since GPN neurones are thought to provide NO-mediated efferent inhibition of the carotid body (CB), these channels
may contribute to the regulation of breathing during hypoxia via negative feedback control of CB function, as well as to the
inhibitory effect of volatile anaesthetics (e.g. halothane) on respiration.