Vanadate: Non-selective inhibition of transepithelial transport of Na+, H+ and water

Summary In the isolated urinary bladder of the toad, 10^–5–10^–4M orthovanadate produces inhibition of the active transport of Na⁺ and H⁺ ions as well as of antidiuretic hormone-mediated osmotic flow of water. Since transport of H⁺ ions and osmotic water flow are not inhibited when (Na⁺+K⁺)-ATPase is inhibited by ouabain, biological actions of vanadate are not necessarily related to inhibition of (Na⁺+K⁺)-ATPase.This research was supported by grant AM-14915 from the National Institutes of Helath.     

The effects of triaminopyrimidine on the short circuit current and transmembrane potentials of the isolated rat visceral yolk sac in vitro

Summary Intracellular potentials in the cells from 17.5-day old rat visceral yolk sacs were measured by a glass microelectrode. When penetrated from the maternal side, the cells have potentials of about 50.2±1.9 mV (inside negative) which were reduced by increasing the external K⁺ concentration and increased by removing Na⁺ ions from the bathing fluid. Triaminopyrimidine (TAP) which inhibited Na⁺ transport caused a dose-dependent depolarization of the cell membrane. The depolarization was dependent on the presence of extracellular Ca²⁺ ions. It is proposed that TAP may inhibit Na⁺ transport by increasing the intracellular concentration of calcium ions.This work was supported by the University of Hong Kong (grant number 335. 034.5105).Acknowledgment. Triaminopyrimidine was synthesized by Dr. Barbara Roth of the Wellcome Research Laboratories.     

Na+,K+-ATPase as a docking station: protein–protein complexes of the Na+,K+-ATPase

The Na⁺,K⁺-ATPase, or sodium pump, is well known for its role in ion transport across the plasma membrane of animal cells. It carries out the transport of Na⁺ ions out of the cell and of K⁺ ions into the cell and thus maintains electrolyte and fluid balance. In addition to the fundamental ion-pumping function of the Na⁺,K⁺-ATPase, recent work has suggested additional roles for Na⁺,K⁺-ATPase in signal transduction and biomembrane structure. Several signaling pathways have been found to involve Na⁺,K⁺-ATPase, which serves as a docking station for a fast-growing number of protein interaction partners. In this review, we focus on Na⁺,K⁺-ATPase as a signal transducer, but also briefly discuss other Na⁺,K⁺-ATPase protein–protein interactions, providing a comprehensive overview of the diverse signaling functions ascribed to this well-known enzyme.     

Experimentelle Feststellung dualer Potentiale an intra-nicht-permutierenden Membranen

Summary It has been shown experimentally that two different potentials appear across an intra-nonpermutating membrane³ when two different solutions (e.g., solution I: 0.1n NaCl+0.0001n KCl; and, solution II: 0.1n KCl + 0.0001n NaCl) are separated by such a membrane, and when the pores of the intra-nonpermutating membrane are supplied with ions from either solution I or solution II (in this case: essentially with Na⁺ ions from solution I, or essentially with K⁺ ions from solution II). The theoretical background, and other considerations, for these experiments will be found in reference.     

Direct inhibition of phospholipid scrambling activity in erythrocytes by potassium ions

The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K⁺] and selective K⁺ channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes decreases by ~50% when the intracellular [K⁺] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling is inducible by raising the intracellular [Ca²⁺] and that K⁺ ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage and microvesicle formation, processes that are generally attributed to Ca²⁺-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca²⁺-sensitive K⁺ channels causes loss of intracellular K⁺ that results in reduced intrinsic inhibitory effect of these ions on scramblase activity. Received 11 September 2008; received after revision 17 October 2008; accepted 27 October 2008     

Groupements sulfhydriques de l'haptoglobine et de sa combinaison hémoglobinique

Summary Free and masked SH groups were determined in haptoglobine (Hp) haemoglobine (Hb) (horse) and in their complex (Hb-Hp). Hp contains no free SH groups, but up to 9 groups are liberated per mol on denaturation by guanidine. The Hb-Hp complex reacts with the same number of Hg⁺⁺ ions as free Hb, but it reacts with one less Ag⁺ ion than free Hb. The 4th Ag⁺ ion is taken up only in the presence of low concentration of a denaturing agent. Hg⁺⁺, Ag⁺, Cu⁺⁺ pcmb and iodine do not inhibit the association of Hb and Hp nor do they diminish the peroxidasic activity of the complex. Sh groups of Hb do not seem to be involved in these two reactions.     

Enhancement of barium- and cesium-induced adrenal catecholamine release by lidocaine

Summary Catecholamine release evoked from isolated perfused bovine adrenals by Ba⁺² or Cs⁺ is enhanced by lidocaine or by a calcium-free medium. The action of Cs⁺ therefore differs from that of K⁺ or Rb⁺ in adrenal medulla. Divalent and monovalent metallic cations of relatively large atomic weight like Ba⁺² and Cs⁺, probably penetrate the cell more easily than small highly charged ions and act intracellularly to cause adrenal catecholamine release. Local anesthetics and calcium-free media may allow greater influx of Ba⁺² and Cs⁺ into adrenomedullary cells.Acknowledgment. This work was supported by NIH, grant No. AM16153.     

Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

In the present study we demonstrated that neurotoxin MPP⁺-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP⁺-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G₀/G₁ cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP⁺ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP⁺ and cell-cycle re-entry through retinoblastoma protein phosphorylation.     

Monovalent cation conductance in liposomes induced by ionophore A23187

Summary In the absence of divalent cations, ionophore A23187 supports low rates of monovalent cations loss (Na⁺>K⁺) from unilamellar liposomes containing the sulfate salts. Monovalent cation efflux is optimal when a pH gradient (interior alkaline) is applied. The maximum observed rate of 0.56 ngion K⁺·min^–1·nmole^–1 A23187 is insufficient to account for the rates of K⁺ efflux induced by the ionophore in mitochondria (150 ngion K⁺·min^–1·nmole^–1 A23187). These studies therefore support the concept that A23187 induces loss of K⁺ from mitochondria by removal of regulating divalent cations from an endogenous K⁺/H⁺ exchanger.These studies were supported in part by United States Public Health Services Grant HL09364.     

Réversibilité de la réponse du potentiel de membrane chezNitella flexilis L. à des variations de pH

Summary The better the recovering of the membrane potential ofNitella on restoring the initial value of the external pH after a change, the more acid is the pH of the medium (Table I). On the other hand, a better repeatability was observed in alkaline solutions (Table II) for a change in the external K⁺ concentration. These results are interpreted as a manifestation of the binding of K⁺ ions to ionizable fixed charges (pK about 5–6) at the membrane surface and of the control of molecular structure of the membrane by the pH.     

Cardiac cellular electrophysiology: past and present

Summary The time-course of the cardiac action potential can be accounted for in terms of ionic currents crossing the cell membranes. Depolarizing current is carried by Na⁺ or Ca²⁺ entering the cells, repolarizing current by K⁺ leaving the cells. Membrane permeability for the passive movement of these ions is thought to be voltage-dependent as well as time-dependent. Net transfer of charge may also result from active transport, 2 Na⁺ out against 1 K⁺ in; or coupled exchange, 3 or 4 Na⁺ in against 1 Ca²⁺ out. This review follows the path by which present-day knowledge has been reached. It also gives a few examples to illustrate that electrophysiology has provided concepts useful to clinical cardiology.     

Biological effects of lithium: Experimental analysis in plant cytokinesis

Summary The biological effects of lithium ions have been studied, using plant cytokinesis in onion root meristems as the experimental model. Lithium induces binucleate cells by inhibiting cell plate formation. Moreover, lithium and caffeine have additive effects on the induction of binucleate cells. Na⁺, K⁺, Ca⁺⁺ and Mg⁺⁺ antagonize lithium-induced inhibition of cytokinesis.     

Inhibition of hepatic Na+, K+-adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat

Summary Na⁺, K⁺-adenosinetriphosphatase (Na⁺, K⁺-ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 moles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10–1300 M) caused significant and dose dependent reductions of Na⁺, K⁺-ATPase activity at taurolithocholate concentrations above 100 M. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na⁺, K⁺-ATPase activity.This work was supported by the Swiss National Science Foundation.The authors thank Mr H. Sägesser and Miss B. Schütz for technical assistance.     

Electrophysiological characteristics ofBombyx mori L. ventral nerve cord (effect of sodium and potassium on the membrane potential)

Summary Na⁺ and K⁺ effects on the resting cellular membrane potential of desheathed ganglia of theBombyx mori L. ventral nerve cord have been studied. The cells are depolarized by high concentrations of external potassium ions in the same way as in vertebrates, mollusca and crustacean cells. The possibility that the behaviour of the resting potential is not only influenced by the potassium equilibrium potential, but also by the conductances to other ions, is discussed.The authors are indebted to Prof V. Capraro, Drs B. Giordana and F. Sacchi for helpful comments and criticism.     

Structural variations in wheat HKT1;5 underpin differences in Na<Superscript>+</Superscript> transport capacity

An important trait associated with the salt tolerance of wheat is the exclusion of sodium ions (Na⁺) from the shoot. We have previously shown that the sodium transporters TmHKT1;5-A and TaHKT1;5-D, from Triticum monoccocum (Tm) and Triticum aestivum (Ta), are encoded by genes underlying the major shoot Na⁺-exclusion loci Nax1 and Kna1, respectively. Here, using heterologous expression, we show that the affinity (K _m) for the Na⁺ transport of TmHKT1;5-A, at 2.66 mM, is higher than that of TaHKT1;5-D at 7.50 mM. Through 3D structural modelling, we identify residues D⁴⁷¹/a gap and D⁴⁷⁴/G⁴⁷³ that contribute to this property. We identify four additional mutations in amino acid residues that inhibit the transport activity of TmHKT1;5-A, which are predicted to be the result of an occlusion of the pore. We propose that the underlying transport properties of TmHKT1;5-A and TaHKT1;5-D contribute to their unique ability to improve Na⁺ exclusion in wheat that leads to an improved salinity tolerance in the field.     

Differences in membrane ion transport between hepatocytes from the periportal and the pericentral areas of the liver lobule

We studied the Na⁺/K⁺ pump, Na⁺/K⁺ ATPase activity, and oxygen consumption (QO₂) in hepatocytes isolated from the periportal (PH) and pericentral (CH) regions of the liver lobule, to provide an insight into the functional properties of these cells. Na⁺/K⁺ pump activity was determined using⁸⁶Rb⁺ (a functional analog of K⁺) and ouabain, a specific inhibitor of this transport system. Our results indicate the the Na⁺/K⁺, pump and Na⁺/K⁺ ATPase activity are significantly lower in CH than in PH, although basal ouabain-sensitive (OS) QO₂ was negligible in both of these cell preparations. However, OSQO₂ was significantly lower in CH than in PH when the Na⁺/K⁺ pump was activated using the ionophore nystatin in a Na⁺-containing medium. These results indicate that the differences in membrane ion transport exist between hepatocytes from different locations of the liver lobule.     

Mesures en continu et in situ des pH artériel et veineux profonds chez le Mammifère

Summary An original pH-probe now permits continuous and in situ control of H⁺ ions in the blood vessels of mammals, especially during hypercapnic conditions.     

Na+ mechanism of δ-opioid receptor induced protection from anoxic K+ leakage in the cortex

Activation of δ-opioid receptors (DOR) attenuates anoxic K⁺ leakage and protects cortical neurons from anoxic insults by inhibiting Na⁺ influx. It is unknown, however, which pathway(s) that mediates the Na⁺ influx is the target of DOR signal. In the present work, we found that, in the cortex, (1) DOR protection was largely dependent on the inhibition of anoxic Na⁺ influxes mediated by voltage-gated Na⁺ channels; (2) DOR activation inhibited Na⁺ influx mediated by ionotropic glutamate N-methyl-D-aspartate (NMDA) receptors, but not that by non-NMDA receptors, although both played a role in anoxic K⁺ derangement; and (3) DOR activation had little effect on Na⁺/Ca²⁺ exchanger-based response to anoxia. We conclude that DOR activation attenuates anoxic K⁺ derangement by restricting Na⁺ influx mediated by Na⁺ channels and NMDA receptors, and that non-NMDA receptors and Na⁺/Ca²⁺ exchangers, although involved in anoxic K⁺ derangement in certain degrees, are less likely the targets of DOR signal. Received 26 November 2008; received after revision 26 December 2008; accepted 13 January 2009     

Enhanced excitability in locust muscle fibres induced by calcium free saline

Summary The membrane of locust muscle fibres normally exhibits a graded electrical response to outward current pulses of increasing strength. On removal of Ca⁺⁺ ions from the external medium, these fibres are shown to exhibit depolarizing membrane responses of variable time course and duration. These responses are abolished in Na⁺-free solutions, and by the addition of Mn⁺⁺ ions.D.A.M. was the recipient of a Royal Society and Science Research Council European Exchange Fellowship. We thank the Centre for Overseas Pest Research, Kensington for supplying the locusts.     

Die katalytische Mutation der Ionen Al3+ und MoO

Summary The catalytic mutation of the ions Al³⁺ and MoO ₄ ^2– on the mixed carrier Cd(OH)₂/Co(OH)₂(Tr) is recognizable by the fact that the combination Tr+Al³⁺+MoO ₄ ^2– is more active in the decomposition of H₂O₂ than the combination Tr+MoO ₄ ^2– +Al³⁺.