A novel O2-sensing mechanism in rat glossopharyngeal neurones mediated by a halothane-inhibitable background K+ conductance.
Modulation of K+ channels by hypoxia is a common O2-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 O2-sensing in certain cell types. Here, we report a novel O2 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 mM TEA, 5 mM 4-aminopyridine (4-AP) and 200 microM Cd2+, but was reversibly inhibited by hypoxia (O2 tension (PO2) = 15 mmHg), 2-5 mM halothane, 10 mM barium and 1 mM 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 microM) caused membrane hyperpolarisation and potentiation of the background K+ current. This pharmacological profile suggests the O2-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.
Campanucci
Verónica A
VA
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1.
Fearon
Ian M
IM
Nurse
Colin A
CA
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D063388:Endocannabinoids; D005930:Glossopharyngeal Nerve / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D012430:Ruthenium Red; D008058:Dihydrolipoamide Dehydrogenase; D006221:Halothane; C078814:anandamide