High-Affinity Zinc Potentiation of Inhibitory Postsynaptic Glycinergic Currents in the Zebrafish Hindbrain

2001 ◽  
Vol 85 (2) ◽  
pp. 912-925 ◽  
Author(s):  
Hiroshi Suwa ◽  
Louis Saint-Amant ◽  
Antoine Triller ◽  
Pierre Drapeau ◽  
Pascal Legendre
Keyword(s):  
Heavy Metals ◽  
Physiological Role ◽  
Synaptic Cleft ◽  
Dissociation Rate ◽  
Apparent Affinity ◽  
Zinc Binding Site ◽  
Zinc Concentrations ◽  
Kinetics Of ◽  
Whole Cell Recordings

Zinc has been reported to potentiate glycine receptors (GlyR), but the physiological significance of this observation has been put in doubt by the relatively high values of the EC50, 0.5–1 μM, since such concentrations may not be attained in the synaptic cleft of glycinergic synapses. We have re-evaluated this observation in the frame of the hypothesis that contaminant heavy metals present in usual solutions may have lead to underestimate the affinity of the zinc binding site, and therefore to underestimate the potential physiological role of zinc. Using chelators either to complex heavy metals or to apply zinc at controlled concentrations, we have examined the action of zinc on GlyR kinetics in outside-out patches from 50-h-old zebrafish Mauthner cells. Chelating contaminating heavy metals with tricine or N,N,N′,N′-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) decreased the duration of the currents evoked by glycine, confirming that traces of heavy metals alter the GlyR response in control conditions. Using tricine- (10 mM) buffered zinc solution, we then showed that zinc increases the amplitude of outside-out responses evoked by 0.1–0.5 mM glycine with an EC50 of 15 nM. In contrast zinc had no effect on the amplitude of currents evoked by a saturating concentration (3–10 mM) of glycine. This suggests that zinc enhances GlyR apparent affinity for glycine. The study of the effects of zinc on the kinetics of the response indicates that this increase of apparent affinity is due to a decrease of the glycine dissociation rate constant. We then analyzed the effects of zinc on postsynaptic GlyRs in whole cell recordings of glycinergic miniature inhibitory postsynaptic currents (mIPSCs). Chelation of contaminant heavy metals decreased the amplitude and the duration of the mIPSCs; inverse effects were observed by adding zinc in buffered solutions containing nanomolar free zinc concentrations. Zinc plus tricine or tricine alone did not change the coefficient of variation (≈0.85) of the mIPSC amplitude distributions. These results suggest that postsynaptic GlyRs are not saturated after the release of one vesicle.

A physiological role of epidermal growth factor in cell kinetics of gastric epithelium

Life Sciences ◽  
1993 ◽  
Vol 52 (13) ◽  
pp. 1135-1139 ◽  
Author(s):  
Koichi Tasaki ◽  
Keisuke Nakata ◽  
Yuji Kato ◽  
Khaleque Newaz Khan ◽  
Satoru Mitsuoka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Kinetics ◽  
Physiological Role ◽  
Gastric Epithelium ◽  
Epidermal Growth ◽  
Kinetics Of

scholarly journals MeCP2 Is Required for Normal Development of GABAergic Circuits in the Thalamus

2010 ◽  
Vol 103 (5) ◽  
pp. 2470-2481 ◽  
Author(s):  
Zhong-Wei Zhang ◽  
Joseph D. Zak ◽  
Hong Liu
Keyword(s):  
Neurodevelopmental Disorder ◽  
Brain Slices ◽  
Inhibitory Neurons ◽  
Gene Encoding ◽  
Vertebrate Brain ◽  
Gabaergic Synapses ◽  
And Function ◽  
Kinetics Of ◽  
Whole Cell Recordings

Methyl-CpG binding protein 2 (MeCP2) is highly expressed in neurons in the vertebrate brain, and mutations of the gene encoding MeCP2 cause the neurodevelopmental disorder Rett syndrome. This study examines the role of MeCP2 in the development and function of thalamic GABAergic circuits. Whole cell recordings were carried out in excitatory neurons of the ventrobasal complex (VB) of the thalamus and in inhibitory neurons of the reticular thalamic nucleus (RTN) in acute brain slices from mice aged P6 through P23. At P14–P16, the number of quantal GABAergic events was decreased in VB neurons but increased in RTN neurons of Mecp2-null mice, without any change in the amplitude or kinetics of quantal events. There was no difference between mutant and wild-type mice in paired-pulse ratios of evoked GABAergic responses in the VB or the RTN. On the other hand, unitary responses evoked by minimal stimulation were decreased in the VB but increased in the RTN of mutants. Similar changes in the frequency of quantal events were observed at P21–P23 in both the VB and RTN. At P6, however, quantal GABAergic transmission was altered only in the VB not the RTN. Immunostaining of vesicular GABA transporter showed opposite changes in the number of GABAergic synaptic terminals in the VB and RTN of Mecp2-null mice at P18–P20. The loss of MeCP2 had no significant effect on intrinsic properties of RTN neurons recorded at P15–P17. Our findings suggest that MeCP2 differentially regulates the development of GABAergic synapses in excitatory and inhibitory neurons in the thalamus.

scholarly journals The substrate specificity of acid α-glucosidase from rabbit muscle

1971 ◽  
Vol 124 (4) ◽  
pp. 701-711 ◽  
Author(s):  
T. N. Palmer
Keyword(s):  
Substrate Inhibition ◽  
Physiological Role ◽  
Liver Glycogen ◽  
Rabbit Muscle ◽  
Ph Optimum ◽  
Enzyme Action ◽  
Rate Limiting ◽  
Kinetics Of ◽  
Hydrolysis Of

1. Acid α-glucosidase was purified 3500-fold from rabbit muscle. 2. The enzyme was activated by cations, the degree of activation varying with the substrate. Enzyme action on glycogen was most strongly activated and activation was apparently of a non-competitive type. With rabbit liver glycogen as substrate, the relative Vmax. increased 15-fold, accompanied by an increase in Km from 8.3 to 68.6mm-chain end over the cation range 2–200mm-Na+ at pH4.5. Action on maltose was only moderately activated (1.3-fold, non-competitively) and action on maltotriose was marginally and competitively inhibited. 3. The pH optimum at 2mm-Na+ was 4.5 (maltose) and 5.1 (glycogen). Cation activation of enzyme action on glycogen was markedly pH-dependent. At 200mm-Na+, the pH optimum was 4.8 and activity was maximally stimulated in the range pH4.5–3.3. 4. Glucosidase action on maltosaccharides was associated with pronounced substrate inhibition at concentrations exceeding 5mm. Of the maltosaccharides tested, the enzyme showed a preference for p-nitrophenyl α-maltoside (Km 1.2mm) and maltotriose (Km 1.8mm). The extrapolated Km for enzyme action on maltose was 3.7mm. 5. The macromolecular polysaccharide substrate glycogen differed from linear maltosaccharide substrates in the kinetics of its interaction with the enzyme. Activity was markedly dependent on pH, cation concentration and polysaccharide structure. There was no substrate inhibition. 6. The enzyme exhibited constitutive α-1,6-glucanohydrolase activity. The Km for panose was 20mm. 7. The enzyme catalysed the total conversion of glycogen into glucose. The hydrolysis of α-1,6-linkages was apparently rate-limiting during the hydrolysis of glycogen. 8. Enzyme action on glycogen and maltose released the α-anomer of d-glucose. 9. The results are discussed in terms of the physiological role of acid α-glucosidase in lysosomal glycogen catabolism.

scholarly journals Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl−/HCO3− exchanger

2016 ◽  
Vol 147 (5) ◽  
pp. 423-436 ◽  
Author(s):  
Gaspar Peña-Münzenmayer ◽  
Alvin T. George ◽  
Gary E. Shull ◽  
James E. Melvin ◽  
Marcelo A. Catalán
Keyword(s):  
Ion Transport ◽  
Physiological Role ◽  
Acinar Cells ◽  
Monovalent Cation ◽  
Ion Concentration ◽  
Secretory Cells ◽  
Whole Cell ◽  
Na Ions ◽  
Whole Cell Recordings

Ae4 (Slc4a9) belongs to the Slc4a family of Cl−/HCO3− exchangers and Na+-HCO3− cotransporters, but its ion transport cycle is poorly understood. In this study, we find that native Ae4 activity in mouse salivary gland acinar cells supports Na+-dependent Cl−/HCO3− exchange that is comparable with that obtained upon heterologous expression of mouse Ae4 and human AE4 in CHO-K1 cells. Additionally, whole cell recordings and ion concentration measurements demonstrate that Na+ is transported by Ae4 in the same direction as HCO3− (and opposite to that of Cl−) and that ion transport is not associated with changes in membrane potential. We also find that Ae4 can mediate Na+-HCO3− cotransport–like activity under Cl−-free conditions. However, whole cell recordings show that this apparent Na+-HCO3− cotransport activity is in fact electroneutral HCO3−/Na+-HCO3− exchange. Although the Ae4 anion exchanger is thought to regulate intracellular Cl− concentration in exocrine gland acinar cells, our thermodynamic calculations predict that the intracellular Na+, Cl−, and HCO3− concentrations required for Ae4-mediated Cl− influx differ markedly from those reported for acinar secretory cells at rest or under sustained stimulation. Given that K+ ions share many properties with Na+ ions and reach intracellular concentrations of 140–150 mM (essentially the same as extracellular [Na+]), we hypothesize that Ae4 could mediate K+-dependent Cl−/HCO3− exchange. Indeed, we find that Ae4 mediates Cl−/HCO3− exchange activity in the presence of K+ as well as Cs+, Li+, and Rb+. In summary, our results strongly suggest that Ae4 is an electroneutral Cl−/nonselective cation–HCO3− exchanger. We postulate that the physiological role of Ae4 in secretory cells is to promote Cl− influx in exchange for K+(Na+) and HCO3− ions.

Asynchronous Generation Of Kinin And Kallikrein Activity Following Soluble Activation Of Plasma

1981 ◽  
Author(s):  
A M Bubnic ◽  
T R Zuffi ◽  
M A Fournel
Keyword(s):  
Generation Time ◽  
Animal Studies ◽  
Dextran Sulfate ◽  
Physiological Role ◽  
Factor Xii ◽  
Kallikrein Activity ◽  
Kinetics Of

In an effort to assess the physiological significance of a soluble activator of Factor XII, the kinetics of F. XII and prekallikrein activation and subsequent kinin formation have been investigated using dextran sulfate. Employing an amidolytic assay for kallikrein and a bioassay for kinin activity a reproducible lag in the generation of detectable kallikrein activity has been demonstrated in the presence of explosive kinin generation. Time, temperature and concentration kinetics have been determined as well as characterization of this system with prekallikrein activator (PKA; B-XIIa; XIIf), selective inhibitors and deficient plasmas. These studies have shown that kinin activity is generated in substantial amounts prior to the generation of any significant kallikrein activity by the activation of F. XII, suggesting that the physiological role of prekallikrein activation in kinin generation may be relatively minor. In vivo animal studies with PKA appear to confirm this finding with insignificant alterations in prekallikrein titers in the presence of marked systemic kinin-mediated hypotension.

COPPER AND ZINC INDUCED CHANGES IN SOYBEAN (Glycine max (L.) Merr.)

1970 ◽  
pp. 09
Author(s):  
K. SANKAR GANESH ◽  
P. SUNDARAMOORTHY
Keyword(s):  
Heavy Metals ◽  
Glycine Max ◽  
Aquatic Environment ◽  
Morphological Traits ◽  
Industrial Activities ◽  
Copper And Zinc ◽  
Glycine Max L ◽  
Zinc Concentrations ◽  
Induced Changes

Heavy metals are one of the most important pollutants released to the aquatic environment by the various industrial activities. The use of these wastewater for irrigation results accumulation of heavy metals in soil and plants. So, the present investigation deals with the various concentrations (0, 5, 10, 25, 50, 100, 200 and 300 mg/l) of copper and zinc on germination studies of soybean. The different concentrations of copper and zinc were used for germination studies. The seedlings were allowed to grow upto seven days. The studied morphological traits increased at 5 mg/l concentration and these parameters are gradually decreased with the increase of copper and zinc concentrations.

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