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      Carotid body chemosensory responses in mice deficient of TASK channels

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          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.

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          Two's company, three's a crowd: can H2S be the third endogenous gaseous transmitter?

          Rui Wang (2002)
          Bearing the public image of a deadly "gas of rotten eggs," hydrogen sulfide (H2S) can be generated in many types of mammalian cells. Functionally, H2S has been implicated in the induction of hippocampal long-term potentiation, brain development, and blood pressure regulation. By acting specifically on KATP channels, H2S can hyperpolarize cell membranes, relax smooth muscle cells, or decrease neuronal excitability. The endogenous metabolism and physiological functions of H2S position this gas well in the novel family of endogenous gaseous transmitters, termed "gasotransmitters." It is hypothesized that H2S is the third endogenous signaling gasotransmitter, besides nitric oxide and carbon monoxide. This positioning of H2S will open an exciting field-H2S physiology-encompassing realization of the interaction of H2S and other gasotransmitters, sulfurating modification of proteins, and the functional role of H2S in multiple systems. It may shed light on the pathogenesis of many diseases related to the abnormal metabolism of H2S.
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            Acute oxygen-sensing mechanisms.

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              Breathing: rhythmicity, plasticity, chemosensitivity.

              Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBötzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.
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                Author and article information

                Journal
                J Gen Physiol
                J. Gen. Physiol
                jgp
                The Journal of General Physiology
                The Rockefeller University Press
                0022-1295
                1540-7748
                April 2010
                : 135
                : 4
                : 379-392
                Affiliations
                Instituto de Biomedicina de Sevilla (IBIS) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla, 41013 Sevilla, Spain
                Author notes
                Correspondence to José López-Barneo: lbarneo@ 123456us.es

                P. Ortega-Sáenz and K.L. Levitsky contributed equally to this paper.

                Article
                200910302
                10.1085/jgp.200910302
                2847918
                20351062
                92064a5b-f4a9-4ba3-8f60-349ee6723049
                © 2010 Ortega-Sáenz et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 20 July 2009
                : 22 February 2010
                Categories
                Article

                Anatomy & Physiology
                Anatomy & Physiology

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