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 m m TEA, 5 m m 4-aminopyridine (4-AP) and 200 μ m Cd²⁺, but was reversibly inhibited by hypoxia (O₂ tension ( P _O2) = 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 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.