Neuronal efflux of noradrenaline induced by tris or lithium as substitutes for extracellular sodium

1986 ◽  
Vol 333 (1) ◽  
pp. 13-16 ◽  
Author(s):  
H. B�nisch ◽  
A. Langeloh
Keyword(s):  
Efflux Of Noradrenaline ◽  
Neuronal Efflux ◽  
Extracellular Sodium

Correlation Between Noradrenaline Fluxes, Metabolism and Compartmentalisation in Human Platelets

1982 ◽  
Vol 48 (01) ◽  
pp. 062-066 ◽  
Author(s):  
Chantal Legrand ◽  
Véronique Dubernard ◽  
Philippe Meyer
Keyword(s):  
Noradrenaline Release ◽  
Human Platelets ◽  
Release Of Noradrenaline ◽  
Storage Pool ◽  
Platelet Storage ◽  
Efflux Of Noradrenaline ◽  
Preferential Localization

Summary(3H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.

scholarly journals Structural and functional analysis of the Na+/H+ exchanger

2007 ◽  
Vol 401 (3) ◽  
pp. 623-633 ◽  
Author(s):  
Emily R. Slepkov ◽  
Jan K. Rainey ◽  
Brian D. Sykes ◽  
Larry Fliegel
Keyword(s):  
Intracellular Ph ◽  
Sequence Similarity ◽  
Structural Data ◽  
Structural Similarity ◽  
Integral Membrane Protein ◽  
Volume Control ◽  
Amino Acid Residues ◽  
Physiological Processes ◽  
High Resolution Structure ◽  
Extracellular Sodium

The mammalian NHE (Na+/H+ exchanger) is a ubiquitously expressed integral membrane protein that regulates intracellular pH by removing a proton in exchange for an extracellular sodium ion. Of the nine known isoforms of the mammalian NHEs, the first isoform discovered (NHE1) is the most thoroughly characterized. NHE1 is involved in numerous physiological processes in mammals, including regulation of intracellular pH, cell-volume control, cytoskeletal organization, heart disease and cancer. NHE comprises two domains: an N-terminal membrane domain that functions to transport ions, and a C-terminal cytoplasmic regulatory domain that regulates the activity and mediates cytoskeletal interactions. Although the exact mechanism of transport by NHE1 remains elusive, recent studies have identified amino acid residues that are important for NHE function. In addition, progress has been made regarding the elucidation of the structure of NHEs. Specifically, the structure of a single TM (transmembrane) segment from NHE1 has been solved, and the high-resolution structure of the bacterial Na+/H+ antiporter NhaA has recently been elucidated. In this review we discuss what is known about both functional and structural aspects of NHE1. We relate the known structural data for NHE1 to the NhaA structure, where TM IV of NHE1 shows surprising structural similarity with TM IV of NhaA, despite little primary sequence similarity. Further experiments that will be required to fully understand the mechanism of transport and regulation of the NHE1 protein are discussed.

Hypernatremia and Intercalated Disc Edema Synergistically Exacerbate Long QT Syndrome Type 3 Phenotype

2021 ◽  
Author(s):  
Xiaobo Wu ◽  
Gregory S. Hoeker ◽  
Grace Blair ◽  
David Ryan King ◽  
Robert G. Gourdie ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Concentration ◽  
Syndrome Type ◽  
Intercalated Disc ◽  
Long Qt ◽  
Disc Edema ◽  
Cardiac Edema ◽  
Qt Syndrome ◽  
Extracellular Sodium ◽  
Type 3

Background: Cardiac voltage-gated sodium channel gain-of-function prolongs repolarization in the Long-QT Syndrome Type 3 (LQT3). Previous studies suggest that narrowing the perinexus within the intercalated disc, leading to rapid sodium depletion, attenuates LQT3-associated action potential duration (APD) prolongation. However, it remains unknown whether extracellular sodium concentration modulates APD prolongation during sodium channel gain-of-function. We hypothesized that elevated extracellular sodium concentration and widened perinexus synergistically prolong APD in LQT3. Methods and Results: LQT3 was induced with anemone toxin type II (ATXII) in Langendorff-perfused guinea pig hearts (n=20). Sodium concentration was increased from 145 to 160 mM. Perinexal expansion was induced with mannitol or the sodium channel β1-subunit adhesion domain antagonist (βadp1). Epicardial ventricular action potentials were optically mapped. Individual and combined effects of varying clefts and sodium concentrations were simulated in a computational model. With ATXII, both mannitol and βadp1 significantly widened the perinexus and prolonged APD, respectively. The elevated sodium concentration alone significantly prolonged APD as well. Importantly, the combination of elevated sodium concentration and perinexal widening synergistically prolonged APD. Computational modeling results were consistent with animal experiments. Conclusions: Concurrently elevating extracellular sodium and increasing intercalated disc edema prolongs repolarization more than the individual interventions alone in the LQT3. This synergistic effect suggests an important clinical implication that hypernatremia in the presence of cardiac edema can markedly increase LQT3-associated APD prolongation. Therefore, this is the first study to provide evidence of a tractable and effective strategy to mitigate LQT3 phenotype by managing patient sodium levels and preventing cardiac edema.

scholarly journals Role of sodium in ADP- and thrombin-induced megakaryocyte spreading.

1983 ◽  
Vol 96 (5) ◽  
pp. 1234-1240 ◽  
Author(s):  
R M Leven ◽  
W H Mullikin ◽  
V T Nachmias
Keyword(s):  
Membrane Potential ◽  
Intracellular Recording ◽  
Membrane Depolarization ◽  
Sodium Permeability ◽  
Sodium Conductance ◽  
Extracellular Sodium

We investigated the role of sodium in megakaryocyte spreading induced by thrombin and ADP. We found that if extracellular sodium was replaced by lithium, potassium, or choline, spreading was inhibited. When extracellular sodium was present, amiloride or tetrodotoxin inhibited spreading. Using intracellular recording we found spreading to be associated with a permanent membrane depolarization. The extent and rate of thrombin-induced depolarization was reduced when lithium replaced sodium. Unspread cells had an average membrane potential of -44.8 mV. Spread cells had an average membrane potential of -18.46 mV. When choline replaced sodium, or when in the presence of tetrodotoxin and amiloride, the spread cells repolarized, indicating that the depolarization is due to an increase in sodium permeability. Similar treatments did not change the membrane potential of unspread cells. Incubation of megakaryocytes with A23187 together with monensin or methylamine induced spreading. Methylamine occasionally caused spreading by itself, but neither ionophore alone caused spreading. These results indicate that megakaryocyte spreading induced by ADP and thrombin depends on an increase in sodium conductance.

Basolateral ammonium transport by the mouse inner medullary collecting duct cell (mIMCD-3)

2004 ◽  
Vol 287 (4) ◽  
pp. F628-F638 ◽  
Author(s):  
Mary E. Handlogten ◽  
Seong-Pyo Hong ◽  
Connie M. Westhoff ◽  
I. David Weiner
Keyword(s):  
Collecting Duct ◽  
Duct Cell ◽  
Ammonium Transport ◽  
Transport Activity ◽  
Acid Base ◽  
Ammonia Transport ◽  
Medullary Collecting Duct ◽  
Extracellular Sodium ◽  
Permeable Support ◽  
Exchange Activity

The renal collecting duct is the primary site for the ammonia secretion necessary for acid-base homeostasis. Recent studies have identified the presence of putative ammonia transporters in the collecting duct, but whether the collecting duct has transporter-mediated ammonia transport is unknown. The purpose of this study was to examine basolateral ammonia transport in the mouse collecting duct cell (mIMCD-3). To examine mIMCD-3 basolateral ammonia transport, we used cells grown to confluence on permeable support membranes and quantified basolateral uptake of the radiolabeled ammonia analog [14C]methylammonia ([14C]MA). mIMCD-3 cell basolateral MA transport exhibited both diffusive and transporter-mediated components. Transporter-mediated uptake exhibited a Kmfor MA of 4.6 ± 0.2 mM, exceeded diffusive uptake at MA concentrations below 7.0 ± 1.8 mM, and was competitively inhibited by ammonia with a Kiof 2.1 ± 0.6 mM. Transporter-mediated uptake was not altered by inhibitors of Na+-K+-ATPase, Na+-K+-2Cl−cotransporter, K+channels or KCC proteins, by excess potassium, by extracellular sodium or potassium removal or by varying membrane potential, suggesting the presence of a novel, electroneutral ammonia-MA transport mechanism. Increasing the outwardly directed transmembrane H+gradient increased transport activity by increasing Vmax. Finally, mIMCD-3 cells express mRNA and protein for the putative ammonia transporter Rh B-glycoprotein (RhBG), and they exhibit basolateral RhBG immunoreactivity. We conclude that mIMCD-3 cells express a basolateral electroneutral NH4+/H+exchange activity that may be mediated by RhBG.

The role of transmembrane sodium gradient in rabbit ileal smooth muscle: Utilization of harmaline

1985 ◽  
Vol 5 (8) ◽  
pp. 667-671 ◽  
Author(s):  
M. S. Suleiman
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Sodium Concentration ◽  
Exchange Mechanism ◽  
Dependent Manner ◽  
Sodium Gradient ◽  
Extracellular Sodium ◽  
Dose Dependent

Decreasing extracellular sodium concentration was found to produce a contractile response of rabbit ileal smooth muscle. As the concentration decreases, the amplitude of contraction increases, thus producing a dose-dependent curve. Harmaline, a competitor for sodium, was found to inhibit the sodium gradient-dependent contractions in a dose-dependent manner. The results are interpreted as harmaline inhibiting a Na–Ca exchange mechanism present in ileal smooth muscle.

scholarly journals The Ultrastructure of the Perineurium in two Insect Species, Carausius Morosus and Periplaneta Americana

1967 ◽  
Vol 2 (1) ◽  
pp. 119-128
Author(s):  
S. H. P. MADDRELL ◽  
J. E. TREHERNE
Keyword(s):  
Connective Tissue ◽  
Periplaneta Americana ◽  
Fluid Transport ◽  
Insect Species ◽  
Carausius Morosus ◽  
Insect Central Nervous System ◽  
Connective Tissue Sheath ◽  
Extracellular Sodium ◽  
Perineurial Cells ◽  
Cellular Layer

The organization of the perineurium in two insect species (Carausius morosus and Periplaneta americana) has been examined with the electron microscope. In both species this cellular layer has been found to possess an extensive system of tortuous channels between the lateral cell walls. These channels are open at the outer margin adjacent to the fibrous connective-tissue sheath, but appear to be closed at the inner margin by regions of septate desmosomes and/or ‘tight’ junctions. There is an increased surface area at the inner margin of the perineurial cells produced by the presence of long inwardly directed flanges. An electron-dense coat has also been identified on the cytoplasmic side of the type II perineurial cell membranes at points of contact with the underlying extracellular system and at the outer surface adjacent to the connective-tissue sheath. This organization of the perineurium is strikingly similar to that observed in a variety of fluid-secreting epithelia and its possible function in fluid transport is discussed in relation to the available evidence on the physiology of the insect central nervous system. It is suggested, contrary to some earlier suppositions, that the perineurium may not be primarily involved in the control of the extracellular sodium level and that this regulation may be effected at a deeper level in the central nervous tissues.

scholarly journals Ion-water coupling controls class A GPCR signal transduction pathways

2020 ◽  
Author(s):  
Neil J. Thomson ◽  
Owen N. Vickery ◽  
Callum M. Ives ◽  
Ulrich Zachariae
Keyword(s):  
Binding Site ◽  
G Protein ◽  
Signal Transmission ◽  
Water Molecules ◽  
Long Distance ◽  
Protein Binding Region ◽  
Dynamics Simulations ◽  
Key Residues ◽  
Extracellular Sodium ◽  
Communication Pathway

G-protein-coupled receptors (GPCRs) transmit signals across the cell membrane, forming the largest family of membrane proteins in humans. Most GPCRs activate through an evolutionarily conserved mechanism, which involves reorientation of helices and key residues, rearrangement of a hydrogen bonding network mediated by water molecules, and the expulsion of a sodium ion from a protonatable binding site. However, how these components interplay to engage the signal effector binding site remains elusive. Here, we applied information theory to molecular dynamics simulations of pharmaceutically important GPCRs to trace concerted conformational variations across the receptors. We discovered a conserved communication pathway that includes protein residues and cofactors and enables the exchange of information between the extracellular sodium binding site and the intracellular G-protein binding region, coupling the most highly conserved protonatable residues at long distance. Reorientation of internal water molecules was found to be essential for signal transmission along this pathway. By inhibiting protonation, sodium decoupled this connectivity, identifying the ion as a master switch that determines the receptors’ ability to move towards active conformations.

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