Role of TASK2 Potassium Channels Regarding Volume Regulation in Primary Cultures of Mouse Proximal Tubules

Barrière, Hervé; Belfodil, Radia; Rubera, Isabelle; Tauc, Michel; Lesage, Florian; Poujeol, Chantal; Guy, Nicolas; Barhanin, Jacques; Poujeol, Philippe

doi:10.1085/jgp.200308820

Cited by 89 publications

(83 citation statements)

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“…Recently, we showed that Task2 channels stabilize the HCO 3 − reabsorption in kidney proximal tubules and that, consequently, Task2-deficient mice present with metabolic acidosis (23). In addition, Task2 channels are involved in cell volume regulation (24)(25)(26).…”

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confidence: 99%

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Gestreau

Heitzmann

Thomas

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Task2 K + channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2 −/− mice showed disturbed chemosensory function with hypersensitivity to low CO 2 concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2 −/− mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstemspinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O 2 chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface.breathing | central chemoreceptors | K2P | KCNK5 | ventral medullary surface S pontaneous breathing requires feedback controls in which detection of blood gases and pH is critical. At present, there is good understanding of the brainstem topology of respiratory centers, and functional measurements in vitro and in vivo have revealed the basic principles of the neuronal network required for respiratory rhythmogenesis and pattern generation. This network comprises several groups of respiratory neurons forming columns extending from the caudal ventrolateral medulla to the dorsolateral pons (1, 2). The activity of this network must be stable yet permanently adjusted to variations of O 2 , CO 2 , and pH during diverse physiological conditions, e.g., sleep, exercise, or high altitude (3). The precise physiological processes by which pH, CO 2 , and O 2 changes are sensed and translated into the appropriate respiratory neural output are important mechanisms that are still a matter of debate (4, 5). Changes in arterial CO 2 / pH are detected by peripheral chemoreceptors, mainly carotid bodies, and multiple chemoreceptive areas within the brainstem. Among the central chemoreceptive areas, two have attracted most attention: the raphe nuclei and the retrotrapezoid nucleus (RTN) (6, 7). The carotid bodies are the major sensors for acute O 2 changes. However, for longer periods of hypoxia, respiratory adaptation is substantially mediated by central mechanisms (8). The ventrolateral medullary surface comprising the RTN and the parafacial respiratory group (pFRG) has been proposed to contain intrinsically CO 2 -and O 2 -sensing neurons (9-12). Recently, a mouse model that carries a mutation of the transcription factor Phox2b, which causes congenital central hypoventilation syndrome in humans, was engineered. A specific loss of a population of Phox2b-expressing RTN/pFRG neurons ...

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confidence: 99%

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Gestreau

Heitzmann

Thomas

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Especially swelling-activated K ϩ and Cl Ϫ channels as well as volume-sensitive transporters of organic osmolytes (e.g., taurine) are important in the RVD response (16), and it has been estimated that ϳ70% of the loss of osmolytes in Ehrlich ascites tumor cells (EATC) during RVD is due to the loss of KCl (14). Various K ϩ channels have been shown to be implicated in RVD depending on cell type; i.e., 1) Ca 2ϩ -activated small conductance K ϩ (SK) channels (24,42), intermediate conductance K ϩ (IK) channels (3,7,24,25,46), and Big conductance K ϩ (BK) channels (10,23); 2) stretch-activated K ϩ channels; 3) voltage-dependent channels; 4) the MinK channel; and 5) the two-pore domain K ϩ channel (4,(31)(32)(33)(34)(35)37). The volume-sensitive ion channels in EATC are the volume-regulated anion channel (VRAC) (38) and the TWIK-related acid-sensitive K ϩ channel-2 (TASK-2) (22,33,41), which belongs to the family of two-pore domain channels (K 2p ).…”

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“…TASK-2 is sensitive to clofilium (35), independent of intracellular Ca 2ϩ (35,41), and highly sensitive to external pH (21). Besides being the swelling-activated K ϩ channel in EATC, TASK-2 has also been found to be involved in volume regulation in kidney cells (4) and in murine spermatozoa (1). Moreover, TASK-2 has been associated with apoptotic volume decrease in EATC cells following cisplatin exposure (40).…”

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Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation

Kirkegaard

Lambert

Gammeltoft

et al. 2010

American Journal of Physiology-Cell Physiology

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Kirkegaard SS, Lambert IH, Gammeltoft S, Hoffmann EK. Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation. Am J Physiol Cell Physiol 299: C844 -C853, 2010. First published July 14, 2010; doi:10.1152/ajpcell.00024.2010.-The swelling-activated K ϩ currents (I K,vol ) in Ehrlich ascites tumor cells (EATC) has been reported to be through the two-pore domain (K2p), TWIK-related acid-sensitive K ϩ channel 2 (TASK-2). The regulatory volume decrease (RVD), following hypotonic exposure in EATC, is rate limited by IK,vol indicating that inhibition of RVD reflects inhibition of TASK-2. We find that in EATC the tyrosine kinase inhibitor genistein inhibits RVD by 90%, and that the tyrosine phosphatase inhibitor monoperoxo(picolinato)-oxo-vanadate(V) [mpV(pic)] shifted the volume set point for inactivation of the channel to a lower cell volume. Swelling-activated K ϩ efflux was impaired by genistein and the Src kinase family inhibitor 4-amino-5-(4-chloro-phenyl)-7-(t-butyl) pyrazolo [3,4-d]pyrimidine (PP2) and enhanced by the tyrosine phosphatase inhibitor mpV(pic). With the use of the TASK-2 inhibitor clofilium, it is demonstrated that mpV(pic) increased the volumesensitive part of the K ϩ efflux 1.3 times. To exclude K ϩ efflux via a KCl cotransporter, cellular Cl Ϫ was substituted with NO 3 Ϫ . Also under these conditions K ϩ efflux was completely blocked by genistein. Thus tyrosine kinases seem to be involved in the activation of the volumesensitive K ϩ channel, whereas tyrosine phosphatases appears to be involved in inactivation of the channel. Overexpressing TASK-2 in human embryonic kidney (HEK)-293 cells increased the RVD rate and reduced the volume set point. TASK-2 has tyrosine sites, and precipitation of TASK-2 together with Western blotting and antibodies against phosphotyrosines revealed a cell swelling-induced, timedependent tyrosine phosphorylation of the channel. Even though we found an inhibiting effect of PP2 on RVD, neither Src nor the focal adhesion kinase (FAK) seem to be involved. Inhibitors of the epidermal growth factor receptor tyrosine kinases had no effect on RVD, whereas the Janus kinase (JAK) inhibitor cucurbitacin inhibited the RVD by 40%. It is suggested that the cytokine receptor-coupled JAK/STAT pathway is upstream of the swelling-induced phosphorylation and activation of TASK-2 in EATC.cell volume regulation; Janus kinase; volume-sensitive channels

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“…59) TASK-2 has been demonstrated to play a rôle in the regulation of cell volume first in Ehrlich ascites tumour cells and then in proximal tubule cells. 63,64) Studies using a TASK-2 knockout mouse 65) have shown that its genetic ablation leads to metabolic acidosis and hypotension secondary to renal loss of HCO 3 Ϫ . TASK-2 channels are expressed in retrotrapezoid nucleus neurons known to be important in mediating central CO 2 and O 2 chemosensitivity.…”

Section: Effect Of Basolateral Ph O In Microdomains Ofmentioning

confidence: 99%

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

Sandoval

Burgos

Sepúlveda

et al. 2011

Biological & Pharmaceutical Bulletin

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The importance of intracellular pH (pH i ) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH o ), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH o -dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH o in confined spaces of native epithelial tissue.

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Role of TASK2 Potassium Channels Regarding Volume Regulation in Primary Cultures of Mouse Proximal Tubules

Cited by 89 publications

References 19 publications

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

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Role of TASK2 Potassium Channels Regarding Volume Regulation in Primary Cultures of Mouse Proximal Tubules

Cited by 89 publications

References 19 publications

Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity

Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity

Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

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Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity