title: Carotid body chemosensory responses in mice deficient of TASK channels.
abstract: Background K(+) channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in TASK1(-/-) or double TASK1/3(-/-) mice. Patch-clamped TASK1/3-null glomus cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in TASK1(-/-) cells. Sensitivity of background currents to changes of extracellular pH was drastically diminished in TASK1/3-null cells. In contrast with these observations, responsiveness to hypoxia or hypercapnia of either TASK1(-/-) or double TASK1/3(-/-) cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null cells was maintained after pharmacological blockade of maxi-K(+) channels. These data in the TASK-null mouse model indicate that TASK3 channels contribute to the background K(+) current in glomus cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for O(2)/CO(2) sensing in mouse CB cells, TASK3 channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal glomus cells. The ability of TASK1/3(-/-) glomus cells to maintain a powerful response to hypoxia even after blockade of maxi-K(+) channels, suggests the existence of multiple sensor and/or effector mechanisms, which could confer upon the cells a high adaptability to maintain their chemosensory function.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ortega-Sáenz
authors.forename: Konstantin L
authors.initials: KL
authors.lastname: Levitsky
authors.forename: María T
authors.initials: MT
authors.lastname: Marcos-Almaraz
authors.forename: Victoria
authors.initials: V
authors.lastname: Bonilla-Henao
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual
authors.forename: José
authors.initials: J
authors.lastname: López-Barneo
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels