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.

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.

scholarly journals The Rnf complex is a Na+ coupled respiratory enzyme in a fermenting bacterium, Thermotoga maritima

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Martin Kuhns ◽  
Dragan Trifunović ◽  
Harald Huber ◽  
Volker Müller
Keyword(s):  
Electron Transport ◽  
Ion Transport ◽  
Cytoplasmic Membrane ◽  
Thermotoga Maritima ◽  
Physiological Role ◽  
Thermophilic Bacterium ◽  
Respiratory Enzyme ◽  
Membrane Bound ◽  
Reverse Electron Transport

Abstractrnf genes are widespread in bacteria and biochemical and genetic data are in line with the hypothesis that they encode a membrane-bound enzyme that oxidizes reduced ferredoxin and reduces NAD and vice versa, coupled to ion transport across the cytoplasmic membrane. The Rnf complex is of critical importance in many bacteria for energy conservation but also for reverse electron transport to drive ferredoxin reduction. However, the enzyme has never been purified and thus, ion transport could not be demonstrated yet. Here, we have purified the Rnf complex from the anaerobic, fermenting thermophilic bacterium Thermotoga maritima and show that is a primary Na+ pump. These studies provide the proof that the Rnf complex is indeed an ion (Na+) translocating, respiratory enzyme. Together with a Na+-F1FO ATP synthase it builds a simple, two-limb respiratory chain in T. maritima. The physiological role of electron transport phosphorylation in a fermenting bacterium is discussed.

Role of cGMP in Isolated Rat Parotid Acinar Cells

1978 ◽  
Vol 57 (11-12) ◽  
pp. 989-994 ◽  
Author(s):  
J.A. Mangos
Keyword(s):  
Acinar Cells ◽  
Cholinergic Receptors ◽  
Secretory Cells ◽  
Parotid Acinar Cells ◽  
Rat Parotid Gland ◽  
Muscarinic Cholinergic ◽  
Rat Parotid ◽  
Isolated Rat

The role of cGMP as the intracellular mediator of the activation of cholinergic receptors in the secretory cells of the rat parotid gland was investigated in vitro using isolated rat parotid acinar cells. It was demonstrated that this cyclic nucleotide is involved in the intracellular translation of activation of muscarinic cholinergic receptors in these cells.

scholarly journals Muscarinic response in rat lacrimal glands

1986 ◽  
Vol 124 (1) ◽  
pp. 15-32
Author(s):  
A. Marty ◽  
M. G. Evans ◽  
Y. P. Tan ◽  
A. Trautmann
Keyword(s):  
Monovalent Cations ◽  
Muscarinic Agonists ◽  
Isolated Cells ◽  
Whole Cell ◽  
Muscarinic Response ◽  
Conductance Changes ◽  
Na Ions ◽  
Gamma S ◽  
Whole Cell Recordings ◽  
Recent Demonstration

A large variety of responses has been uncovered by recent investigations of conductance changes elicited by muscarinic agonists. In exocrine glands, the permeability to K+, Cl- and Na+ ions is increased, and internal Ca2+ serves as a second messenger. Patch-clamp analysis of the secreting cells has revealed three types of Ca2+-dependent channels, which are respectively selective for K+, for Cl-, and for monovalent cations. The channels differ in their sensitivity to the internal Ca2+ concentration, Cai. K+-selective channels are partially activated at rest, with Cai approx. 10 nmol l-1; Cl(−)-selective channels are activated between 100 nmol l-1 and 1 mumol l-1; activation of cationic channels requires micromolar Cai levels. Cell-attached recordings, performed either on isolated cells or on cell clusters, show an activation of all three channel types upon application of acetylcholine. In whole-cell recordings, mostly K+- and Cl(−)-selective channels are activated. The cell currents display slow oscillations linked to variations of Cai. Whole-cell currents rise after a delay of approx. 1 s, and decay with a time constant of approx. 0.7 s upon removal of acetylcholine. They do not depend on extracellular Ca2+. The recent demonstration that Ca2+-dependent currents can also be obtained when dialysing the cells with inositoltrisphosphate or with GTP gamma S, a non-hydrolysable analogue of guanosine triphosphate, opens promising leads to an analysis of intracellular events regulated by acetylcholine.

A universal mechanism for transport and regulation of CPA sodium proton exchangers

2015 ◽  
Vol 396 (9-10) ◽  
pp. 1091-1096 ◽  
Author(s):  
Octavian Călinescu ◽  
Klaus Fendler
Keyword(s):  
Physiological Role ◽  
Monovalent Cation ◽  
General Mechanism ◽  
Transport Activity ◽  
Dependent Activity ◽  
Regulation Of Transport ◽  
Ph Dependent ◽  
Universal Mechanism ◽  
Single Binding Site

Abstract Recent studies performed on a series of Na+/H+ exchangers have led us to postulate a general mechanism for Na+/H+ exchange in the monovalent cation/proton antiporter superfamily. This simple mechanism employs a single binding site for which both substrates compete. The developed kinetic model is self-regulatory, ensuring down-regulation of transport activity at extreme pH, and elegantly explains the pH-dependent activity of Na+/H+ exchangers. The mechanism was experimentally verified and shown to describe both electrogenic and electroneutral exchangers. Using a small number of parameters, exchanger activity can be modeled under different conditions, providing insights into the physiological role of Na+/H+ exchangers.

Sign in / Sign up

Export Citation Format

Share Document