Role of P5A-Type ATPase in Ion Homeostasis and Signaling: Shedding Light on Obscure Pump

2015 ◽  
pp. 551-565
Author(s):  
Anna L. Okorokova-Façanha ◽  
Antônio Jesus Dorighetto Cogo ◽  
Lívia Marini Palma
Keyword(s):  
Ion Homeostasis

Protective Effect of Ifenprodil Against Spreading Depression in the Mouse Entorhinal Cortex

2004 ◽  
Vol 92 (4) ◽  
pp. 2610-2614 ◽  
Author(s):  
Leonardo Coutinho Faria ◽  
Istvan Mody
Keyword(s):  
Nmda Receptor ◽  
Entorhinal Cortex ◽  
Spreading Depression ◽  
Ion Homeostasis ◽  
Brain Slices ◽  
Nmda Receptor Antagonist ◽  
Cerebrovascular Diseases ◽  
Nr2b Receptor Subunit ◽  
Nr2b Receptor

In the brain, spreading depression (SD) is characterized by a large extracellular DC shift, a massive failure of ion homeostasis and a transient cessation of neuronal function. Clinically, SD is believed to be involved in various neurological disorders including migraine and cerebrovascular diseases. The propagation of cortical SD requires the release of glutamate, and N-methyl-d-aspartate (NMDA) receptors play a crucial role in this process. Here, we have isolated the NMDA receptor-mediated component of extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) in layers 2–3 of the entorhinal cortex of murine brain slices. In the absence of GABAA and AMPA receptor-mediated synaptic transmission, stimulation of layer 6 afferents every 15–90 s elicited spontaneous SD on average within 18.5 min after the start of the stimulation. In the presence of ifenprodil, an NR2B receptor subunit-selective NMDA receptor antagonist, the occurrence of SD was nearly abolished. Our results are consistent with an important role of NR2B subunits in triggering SD in the entorhinal cortex.

scholarly journals Functional modulation of PTH1R activation and signalling by RAMP2

2021 ◽  
Author(s):  
Katarina Nemec ◽  
Hannes Schihada ◽  
Gunnar Kleinau ◽  
Ulrike Zabel ◽  
Eugene O. Grushevskyi ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Critical Role ◽  
Ion Homeostasis ◽  
Optical Biosensors ◽  
Dependent Manner ◽  
Activated State ◽  
Class B ◽  
Receptor Activity Modifying Proteins ◽  
G Protein Coupled

Receptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that associate with different G protein-coupled receptors (GPCRs) including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR, and an important modulator of mineral ion homeostasis and bone metabolism. However, it is unknown whether and how RAMP proteins may affect PTH1R function. Using different optical biosensors to measure the activation of PTH1R and its downstream signalling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique pre-activated state that permits faster activation in a ligand-specific manner. Moreover, RAMP2 modulates PTH1R downstream signalling in an agonist-dependent manner, most notably increasing the PTH-mediated Gi3 signalling sensitivity. Additionally, RAMP2 increases both PTH- and PTHrP-triggered β-arrestin2 recruitment to PTH1R. Employing homology modelling we describe the putative structural molecular basis underlying our functional findings. These data uncover a critical role of RAMPs in the activation and signalling of a GPCR that may provide a new venue for highly specific modulation of GPCR function and advanced drug design.

scholarly journals Critical role of WNK1 in MYC-dependent early mouse thymocyte development

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Robert Köchl ◽  
Lesley Vanes ◽  
Miriam Llorian Sopena ◽  
Probir Chakravarty ◽  
Harald Hartweger ◽  
...  
Keyword(s):  
Critical Role ◽  
Ion Homeostasis ◽  
Thymocyte Development ◽  
Double Positive ◽  
Mouse Thymocyte ◽  
Proliferation And Differentiation ◽  
Tcr Signals ◽  
And Migration ◽  
Early Mouse

WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.

The Role of Glial Cells in Ion Homeostasis in the Retina of the Honeybee Drone

1986 ◽  
pp. 404-413 ◽  
Author(s):  
R. K. Orkand ◽  
J. A. Coles ◽  
M. Tsacopolous
Keyword(s):  
Glial Cells ◽  
Ion Homeostasis ◽  
Honeybee Drone

scholarly journals The novel ECF56 SigG1-RsfG system modulates morphological differentiation and metal-ion homeostasis in Streptomyces tsukubaensis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rute Oliveira ◽  
Matthew J. Bush ◽  
Sílvia Pires ◽  
Govind Chandra ◽  
Delia Casas-Pastor ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Morphological Differentiation ◽  
The Novel ◽  
Copper Trafficking ◽  
Streptomyces Tsukubaensis ◽  
Metal Ion Homeostasis ◽  
Σ Factor ◽  
Domain Organisation

AbstractExtracytoplasmic function (ECF) sigma factors are key transcriptional regulators that prokaryotes have evolved to respond to environmental challenges. Streptomyces tsukubaensis harbours 42 ECFs to reprogram stress-responsive gene expression. Among them, SigG1 features a minimal conserved ECF σ2–σ4 architecture and an additional C-terminal extension that encodes a SnoaL_2 domain, which is characteristic for ECF σ factors of group ECF56. Although proteins with such domain organisation are widely found among Actinobacteria, the functional role of ECFs with a fused SnoaL_2 domain remains unknown. Our results show that in addition to predicted self-regulatory intramolecular amino acid interactions between the SnoaL_2 domain and the ECF core, SigG1 activity is controlled by the cognate anti-sigma protein RsfG, encoded by a co-transcribed sigG1-neighbouring gene. Characterisation of ∆sigG1 and ∆rsfG strains combined with RNA-seq and ChIP-seq experiments, suggests the involvement of SigG1 in the morphological differentiation programme of S. tsukubaensis. SigG1 regulates the expression of alanine dehydrogenase, ald and the WhiB-like regulator, wblC required for differentiation, in addition to iron and copper trafficking systems. Overall, our work establishes a model in which the activity of a σ factor of group ECF56, regulates morphogenesis and metal-ions homeostasis during development to ensure the timely progression of multicellular differentiation.

Role of Na/K/Cl cotransport in astrocytes

1992 ◽  
Vol 70 (S1) ◽  
pp. S260-S262 ◽  
Author(s):  
Wolfgang Walz
Keyword(s):  
Volume Regulation ◽  
Ion Homeostasis ◽  
Combined Cycle ◽  
Kinetic Characterization ◽  
Cultured Astrocytes ◽  
Net Uptake ◽  
Swelling Volume ◽  
External K

The kinetic characterization of the Na/K/Cl cotransport of cultured astrocytes and evidence for its involvement in volume regulation and K+ net uptake during K+ clearance are reviewed. Emphasis is put on experimental evidence for a proposed sodium cycle in astrocytes; this cycle involves a Na+–K+ ATPase that is stimulated by both a high external K+ and intracellular Na+. Elevated external K+ also stimulates the Na/K/Cl carrier, transporting these ions inward. As a result Na+ is cycled across the membrane, carried inward by the Na/K/Cl carrier, and returned by the Na+–K+ ATPase. Both functionally coupled mechanisms lead to intracellular KCl accumulation and inward movements of water to compensate for increased osmolarity. The combined cycle is expected to play a major role in the regulation of physiological K+ levels in the brain.Key words: furosemide, ion homeostasis, Na+–K+ ATPase, swelling, volume regulation.

scholarly journals Functional Aspects of Seminal Plasma in Bird Reproduction

2020 ◽  
Vol 21 (16) ◽  
pp. 5664
Author(s):  
Julian Santiago-Moreno ◽  
Elisabeth Blesbois
Keyword(s):  
Seminal Plasma ◽  
Ion Homeostasis ◽  
Sperm Concentration ◽  
Cellular Functions ◽  
Functional Aspects ◽  
Reproductive Techniques ◽  
Sperm Survival ◽  
Protein Components ◽  
And Function

This review provides an updated overview of the seminal plasma composition, and the role of metabolic and protein components on the sperm function of avian species. In addition, the implication of seminal plasma on assisted reproductive techniques of birds was discussed. The semen of birds usually has exceptionally high sperm concentration with relatively little seminal plasma, but this contributes to very fast changes in sperm metabolism and function. The biochemical characteristics and physiological roles of the various seminal plasma components in birds (carbohydrates, lipids, amino acids, hormones, and proteins) are poorly understood. Seminal plasma content of proteins has an action on most cellular functions: metabolism, immunity, oxido-reduction regulation, proteolysis, apoptosis, ion homeostasis, and antimicrobial defenses. The variable amount of many proteins is related to a different fertility capacity of poultry sperm. The role of seminal plasma on semen conservation (chilling and freezing) remains largely a matter of speculation, as both inhibitory and stimulating effects have been found. Whereas the presence of seminal plasma did not seem to affect the sperm survival after freezing–thawing, DNA fragmentation is lower in the absence of seminal plasma. The molecular basis of the influence of seminal plasma on sperm cryo-resistance was also discussed in the present review.

scholarly journals Coupling of Energy Failure and Dissipative K+ Flux during Ischemia: Role of Preischemic Plasma Glucose Concentration

1993 ◽  
Vol 13 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Anders Ekholm ◽  
Ken-Ichiro Katsura ◽  
Bo K. Siesjö
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Energy State ◽  
Ion Homeostasis ◽  
Plasma Glucose Concentration ◽  
Tissue Temperature ◽  
Ischemic Depolarization ◽  
The Moment ◽  
Tissue Contents

The present experiments were undertaken to assess the influence of preischemic hypo- or hyperglycemia on the coupling among changes in extracellular K+ concentration (K+e) and in cellular energy state, as the latter is reflected in the tissue concentrations of phosphocreatine (PCr), Cr, ATP, ADP, and AMP, and in the calculated free ADP (ADPf) concentrations. The questions posed were whether the final release of K+ was delayed because the extra glucose accumulated by hyperglycemic animals produced enough ATP to continue supporting Na+–K+-driven ATPase activity, and whether the additional acidosis altered the ionic transients. As expected, preischemic hypoglycemia shortened and hyperglycemia prolonged the phase before K+e rapidly increased. This was reflected in corresponding changes in tissue ATP content. Thus, hypoglycemia shortened and hyperglycemia prolonged the time before the fall in ATP concentration accelerated. When tissue was frozen at the moment of depolarization, the tissue contents of ATP were similar in hypo-, normo-, and hyperglycemic groups, ∼ 30% of control. This suggests that hyperglycemia retards loss of ion homeostasis by leading to production of additional ATP. However, hyperglycemia did not reduce the rate at which the PCr concentration fell, and the ATP/ADPf ratio decreased. There were marked differences in the amount of lactate accumulated between the groups. Thus, massive depolarization in hypoglycemic groups occurred at a tissue lactate content of ∼4 m M kg−1. This corresponds to a decrease in intracellular pH (pHi) from ∼7.0 to ∼6.9. In the hyperglycemic groups, depolarization occurred at a lactate content of about 12 mm kg−1, corresponding to a pHi of ∼6.4. This fall in pHi, or the accompanying fall in extracellular pH (pHe), did not affect the maximal rate of efflux of K+. Measurements of ischemic depolarization at constant tissue temperature (37°C) suggest that the influence of the plasma glucose concentration on the terminal depolarization time is restricted. Thus, the time to depolarization varied between 30 s (hypoglycemia) and 90 s (moderate to severe hyperglycemia). Previous results obtained without temperature control may well have reflected a combination between hyperglycemia and a fall in tissue temperature.

scholarly journals Na+/H+Antiport Is Essential for Yersinia pestis Virulence

2013 ◽  
Vol 81 (9) ◽  
pp. 3163-3172 ◽  
Author(s):  
Yusuke Minato ◽  
Amit Ghosh ◽  
Wyatt J. Faulkner ◽  
Erin J. Lind ◽  
Sara Schesser Bartra ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Drug Target ◽  
Deletion Mutant ◽  
Ex Vivo ◽  
Ion Homeostasis ◽  
Content Type ◽  
Double Deletion ◽  
Derivative Strain

ABSTRACTNa+/H+antiporters are ubiquitous membrane proteins that play a central role in the ion homeostasis of cells. In this study, we examined the possible role of Na+/H+antiport inYersinia pestisvirulence and found thatY. pestisstrains lacking the major Na+/H+antiporters, NhaA and NhaB, are completely attenuated in anin vivomodel of plague. TheY. pestisderivative strain lacking thenhaAandnhaBgenes showed markedly decreased survival in blood and blood serumex vivo. Complementation of eithernhaAornhaBintransrestored the survival of theY. pestis nhaA nhaBdouble deletion mutant in blood. ThenhaA nhaBdouble deletion mutant also showed inhibited growth in an artificial serum medium, Opti-MEM, and a rich LB-based medium with Na+levels and pH values similar to those for blood. Taken together, these data strongly suggest that intact Na+/H+antiport is indispensable for the survival ofY. pestisin the bloodstreams of infected animals and thus might be regarded as a promising noncanonical drug target for infections caused byY. pestisand possibly for those caused by other blood-borne bacterial pathogens.

scholarly journals The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization

2017 ◽  
Vol 13 (10) ◽  
pp. e1005804 ◽  
Author(s):  
Niklas Hübel ◽  
Mahshid S. Hosseini-Zare ◽  
Jokūbas Žiburkus ◽  
Ghanim Ullah
Keyword(s):  
Ion Homeostasis ◽  
Spreading Depolarization
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