Molecular Mechanisms of Acid-Base Sensing by the Kidney

Brown, Dennis; Wagner, Carsten A.

doi:10.1681/asn.2012010029

Cited by 80 publications

(64 citation statements)

References 75 publications

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“…The signals for these changes are often thought to be pH per se, either intracellular or extracellular. A variety of pH sensors have also been proposed (25), most notably including nonreceptor tyrosine kinase Pyk2, endothelin B receptor (activated by endogenous renal endothelin) (26,27), and CO 2 activation of ErbB1/2, ERK, and the apical angiotensin I receptor (28). More directly, decreased intracellular pH will increase the availability of protons for H 1 secretion and also, allosterically enhance the Na 1 /H 1 exchanger (29).…”

Section: Regulation Of Hco 3 2 Reabsorption In the Proximal Tubulementioning

confidence: 99%

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Acid-Base Homeostasis

Hamm¹,

Nakhoul²,

Hering-Smith³

2015

Clinical Journal of the American Society of Nephrology

325

262

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Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO 3 2 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO 3 2 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

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Section: Regulation Of Hco 3 2 Reabsorption In the Proximal Tubulementioning

confidence: 99%

“…Increased NH 4 1 excretion is expected as well with chronic respiratory acidosis (83). With the ubiquitous changes that occur in response to acidosis or acid loads, many investigators have looked for acid sensors; a variety of proteins seem to serve some of this function, but no single sensor can be proposed (25).…”

Section: Compensation For Acid-base Disordersmentioning

confidence: 99%

Acid-Base Homeostasis

Hamm¹,

Nakhoul²,

Hering-Smith³

2015

Clinical Journal of the American Society of Nephrology

325

262

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“…11 Pyk2 is a member of the focal adhesion kinase family of tyrosine kinases and its activation is followed by the activation of tyrosine kinase c-Src. 11,12 SENSING CO 2 /HCO 3 2 There are very few CO 2 /HCO 3 2 -sensing molecules that are also expressed in the kidney. One notable molecule is the soluble adenylyl cyclase (sAC; also known as soluble adenyl cyclase 10, ADCY10, or Sacy), which is primarily expressed in the cytoplasm but is also found in the organelles of cells.…”

Section: Sensing Phmentioning

confidence: 99%

“…6 In the kidney, sAC is primarily expressed in cells of the thick ascending loop of Henle, the distal tubule, and the collecting duct. 10,12 Its localization in the proximal tubule remains controversial. An interaction between sAC and Pyk2 has been proposed, which could indicate a potential role for sAC in regulating NHE-3 and NBC-1 in the proximal tubule.…”

Section: Sensing Phmentioning

confidence: 99%

Receptor Protein Tyrosine Phosphatase γ, CO2 Sensing in Proximal Tubule and Acid Base Homeostasis

Soleimani

2016

JASN

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“…Peripheral sensors in the carotid bodies and incompletely defined central chemoreceptors respond to small changes in CO 2 /H + by homeostatically altering the breathing rate (3,20). In concert, pH and HCO 3 − sensors in the kidneys regulate H + and HCO 3 − excretion (21,22). These mechanisms keep human blood pH close to 7.4, and in healthy individuals neurons experience only limited fluctuation in CO 2 /H + .…”

mentioning

confidence: 99%

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

Fenk

Bono

2015

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

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Carbon dioxide (CO 2 ) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO 2 , and previous work identified three neuron pairs called "BAG," "AFD," and "ASE" that respond to CO 2 stimuli. Using in vivo Ca 2+ imaging and behavioral analysis, we show that C. elegans can detect CO 2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO 2 with a rise in Ca 2+ . In contrast, glial sheath cells harboring the sensory endings of C. elegans' major chemosensory neurons exhibit strong and sustained decreases in Ca 2+ in response to high CO 2 . Some of these CO 2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO 2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO 2 . Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO 2 is elevated. CO 2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO 2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO 2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.neural circuit | behavioral choice | olfactory system | oviposition | glia M ost living matter creates temporal or spatial gradients of carbon dioxide (CO 2 ). Animals across phylogeny use such gradients to help detect food, conspecifics, or predators (1, 2). The ubiquity of CO 2 suggests that the ecologically relevant information it communicates will depend on the dynamics of the CO 2 stimulus and on context. CO 2 -responsive excitable cells have been identified in mammals (3), arthropods (4), and nematodes (5, 6). However, the number of CO 2 -responsive neurons that are functional in vivo, how they are embedded in neural circuits, and how they shape behavior is unclear.CO 2 crosses membranes readily and dissolves to generate CO 2 (aq), H + , and HCO 3 − . Many proteins whose activity is modified by CO 2 or its solvation products have been identified. pH changes can modulate G protein-coupled receptors (7), Ca 2+ -activated K + channels (8), inwardly rectifying K + channels (9), two pore domain K + channels (10), transient receptor potential (TRP) channels (11, 12), acid-sensing ion channels (ASICs) (13,14), and Pyk2 and ErbB1/2 kinases (15). HCO 3 − modulates soluble adenylate cyclase (16) and transmembrane guanylate cyclases (17); and CO 2 (aq) has been proposed to regulate transmembrane guanylate cyclases (18) and connexin 26 (19) directly. Cells expressing any of these proteins potentially could transduce changes in CO 2 /H + , raising the question: Do animals use a few specific sensory channe...

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Molecular Mechanisms of Acid-Base Sensing by the Kidney

Cited by 80 publications

References 75 publications

Acid-Base Homeostasis

Acid-Base Homeostasis

Receptor Protein Tyrosine Phosphatase γ, CO2 Sensing in Proximal Tubule and Acid Base Homeostasis

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

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Molecular Mechanisms of Acid-Base Sensing by the Kidney

Cited by 80 publications

References 75 publications

Acid-Base Homeostasis

Acid-Base Homeostasis

Receptor Protein Tyrosine Phosphatase γ, CO2 Sensing in Proximal Tubule and Acid Base Homeostasis

Environmental CO 2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

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Product

Resources

About

Environmental CO ₂ inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity