Cloning and Expression of a Novel pH-sensitive Two Pore Domain K+ Channel from Human Kidney

Reyes, Roberto V.; Duprat, Fabrice; Lesage, Florian; Fink, Michel; Salinas, Miguel; Farman, Nicolette; Lazdunski, Michel

doi:10.1074/jbc.273.47.30863

Cited by 340 publications

(351 citation statements)

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“…Recently, the importance of TASK2 in NaHCO 3 absorption in the proximal tubule has been established, and TASK2-deficient animals have a metabolic acidosis and hypotension (3). TASK2 currents are noninactivating and show no voltage dependence (2). It has also been shown that intracellular sodium causes a concentration-and voltagedependent block of TASK2 channels such that TASK2 demonstrates a weak inward rectification (4).…”

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“…It has also been shown that intracellular sodium causes a concentration-and voltagedependent block of TASK2 channels such that TASK2 demonstrates a weak inward rectification (4). TASK2 currents are inhibited by lidocaine and bupivacaine and potentiated by halothane and chloroform (2). TASK2 is also sensitive to changes in the osmotic potential of the external medium and participates in cell volume regulation (5).…”

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confidence: 99%

“…TASK2 is a member of the tandem-pore domain K ϩ channel (K2P channel) family and is located in various epithelial tissues including the pancreas, placenta, lung, small intestine, colon, and, especially, kidney (2). Recently, the importance of TASK2 in NaHCO 3 absorption in the proximal tubule has been established, and TASK2-deficient animals have a metabolic acidosis and hypotension (3).…”

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pH sensing in the two-pore domain K ⁺ channel, TASK2

Morton

Abohamed

Sivaprasadarao

et al. 2005

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

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TASK2 is a member of the two-pore domain K ؉ channel family that plays a role in acid-base homeostasis; TASK2 knockout animals have plasma electrolyte patterns typical of the human clinical condition of renal tubular acidosis. It is expressed preferentially in epithelia, including the proximal tubules of the kidney. In common with the other TASK channels, TASK2 is sensitive to changes in extracellular pH, although the molecular mechanism of such pH sensing is not understood. We have examined the role of charged residues in the extracellular domains in pH sensing using a mutational approach. Mutant channels were expressed in CHO cells and studied by whole-cell and single-channel patch clamp. Neutralization of no single amino acid in isolation gave complete loss of pH sensitivity. However, the combined removal of five charged amino acids in the large extracellular loop linking the first transmembrane and pore domains, the M1-P1 loop, resulted in an essentially pH-insensitive channel, stabilized in the open state. Wild-type channels contain two such loops, but a concatemeric construct, comprised of one wild-type subunit and one containing the five mutations, was fully pH-sensitive, indicating that only one M1-P1 loop is required to yield a fully pH-sensitive channel, demonstrating a regulatory role of this distinctive structure in two-pore domain K ؉ channels. Thus, pH sensing in TASK2 channels is conferred by the combined action of several charged residues in the large extracellular M1-P1 loop.potassium channel ͉ regulation ͉ acid ͉ proton ͉ gating

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pH sensing in the two-pore domain K ⁺ channel, TASK2

Morton

Abohamed

Sivaprasadarao

et al. 2005

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

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“…Because no or only weak expression of Task2 has been found in the brain (22), this channel has not been considered for cen-tral chemoreception. Task2 has been described as an epithelial channel, abundant in kidney, salivary glands, and the colon.…”

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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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“…Increased cytosolic cAMP inhibits TREK -1 and TREK -2 but not TRAAK (Reyes et al 1998 ;Patel et al 1998 ;. We used forskolin, a direct activator of adenylate cyclase, to increase cAMP in the bladder cells.…”

Section: Effect Of Forskolin On Sac -And Aa -Induced Currentsmentioning

confidence: 99%

Swelling-activated and arachidonic acid-induced currents are TREK-1 in rat bladder smooth muscle cells

Fukasaku

Kimura

Yamaguchi

2016

FJMS

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Using the perforated patch voltage clamp, we investigated swelling -activated ionic channels (SACs) in rat urinary bladder smooth muscle cells. Hypo -osmotic (60%) bath solution increased a membrane current which was inhibited by the SAC inhibitor, gadolinium. The reversal potential of the hypotonicity -induced current shifted in the positive direction by increasing external K + concentration. The hypotonicity -induced current was inhibited by extracellular acidic pH, phorbol ester and forskolin. These pharmacological properties are identical to those of arachidonic acid -induced current present in these cells, suggesting the presence of TREK -1, a four -transmembrane two pore domain K + channel. Using RT -PCR we screened rat bladder smooth muscles and cerebellum for expression of TREK -1, TREK -2 and TRAAK mRNAs. Only TREK -1 mRNA was expressed in the bladder, while all three were expressed in the cerebellum. We conclude that a mechanosensitive K + channel is present in rat bladder myocytes, which is activated by arachidonic acid and most likely is TREK -1. This K + channel may have an important role in the regulation of bladder smooth muscle tone during urine storage.

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Cloning and Expression of a Novel pH-sensitive Two Pore Domain K+ Channel from Human Kidney

Cited by 340 publications

References 43 publications

pH sensing in the two-pore domain K ⁺ channel, TASK2

pH sensing in the two-pore domain K ⁺ channel, TASK2

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

Swelling-activated and arachidonic acid-induced currents are TREK-1 in rat bladder smooth muscle cells

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Cloning and Expression of a Novel pH-sensitive Two Pore Domain K+ Channel from Human Kidney

Cited by 340 publications

References 43 publications

pH sensing in the two-pore domain K + channel, TASK2

pH sensing in the two-pore domain K + channel, TASK2

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

Swelling-activated and arachidonic acid-induced currents are TREK-1 in rat bladder smooth muscle cells

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pH sensing in the two-pore domain K ⁺ channel, TASK2

pH sensing in the two-pore domain K ⁺ channel, TASK2

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