scholarly journals Intracellular Cl− as a signaling ion that potently regulates Na+/HCO3− transporters

2015 ◽  
Vol 112 (3) ◽  
pp. E329-E337 ◽  
Author(s):  
Nikolay Shcheynikov ◽  
Aran Son ◽  
Jeong Hee Hong ◽  
Osamu Yamazaki ◽  
Ehud Ohana ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Mammalian Cells ◽  
Ion Homeostasis ◽  
Transport Processes ◽  
Transepithelial Transport ◽  
High Affinity ◽  
Dependent Site ◽  
Receptor Binding Protein

Cl− is a major anion in mammalian cells involved in transport processes that determines the intracellular activity of many ions and plasma membrane potential. Surprisingly, a role of intracellular Cl− (Cl−in) as a signaling ion has not been previously evaluated. Here we report that Cl−in functions as a regulator of cellular Na+ and HCO3− concentrations and transepithelial transport through modulating the activity of several electrogenic Na+-HCO3− transporters. We describe the molecular mechanism(s) of this regulation by physiological Cl−in concentrations highlighting the role of GXXXP motifs in Cl− sensing. Regulation of the ubiquitous Na+-HCO3− co-transport (NBC)e1-B is mediated by two GXXXP-containing sites; regulation of NBCe2-C is dependent on a single GXXXP motif; and regulation of NBCe1-A depends on a cryptic GXXXP motif. In the basal state NBCe1-B is inhibited by high Cl−in interacting at a low affinity GXXXP-containing site. IP3 receptor binding protein released with IP3 (IRBIT) activation of NBCe1-B unmasks a second high affinity Cl−in interacting GXXXP-dependent site. By contrast, NBCe2-C, which does not interact with IRBIT, has a single high affinity N-terminal GXXP-containing Cl−in interacting site. NBCe1-A is unaffected by Cl−in between 5 and 140 mM. However, deletion of NBCe1-A residues 29–41 unmasks a cryptic GXXXP-containing site homologous with the NBCe1-B low affinity site that is involved in inhibition of NBCe1-A by Cl−in. These findings reveal a cellular Cl−in sensing mechanism that plays an important role in the regulation of Na+ and HCO3− transport, with critical implications for the role of Cl− in cellular ion homeostasis and epithelial fluid and electrolyte secretion.

Membrane Potentials in Amoeba Proteus

1966 ◽  
Vol 45 (2) ◽  
pp. 251-267
Author(s):  
M. S. BINGLEY
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Morphological Changes ◽  
Amoeba Proteus ◽  
Membrane Potentials ◽  
The Other ◽  
The Earth ◽  
Electrode Resistance ◽  
Alternating Voltage

1. Amoebae can be penetrated by microelectrodes at either end. One records voltage and the other supplies alternating current. 2. Step-like increases in alternating voltage superimposed on potentials recorded by the voltage electrode when in either the pseudopod or rear region demonstrate that low potentials recorded from a pseudopod and high ones from the rear region exist across a discrete impedance barrier. The only structure so far shown to fulfil this function is the plasma membrane. 3. A resistance inserted in the earth path monitors current flowing through the system and confirms observations made when recording with single electrodes that there is a reduction of electrode resistance when the cell is entered. 4. Pronounced depolarization in the rear region is shown when the current-carrying electrode penetrates the pseudopod, but not vice versa. 5. Morphological changes associated with membrane potential reversal are illustrated. 6. Consideration is given to the role of step-like potential changes in movement.

scholarly journals Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus

2015 ◽  
Vol 89 (18) ◽  
pp. 9440-9453 ◽  
Author(s):  
Emmanuel Adu-Gyamfi ◽  
Kristen A. Johnson ◽  
Mark E. Fraser ◽  
Jordan L. Scott ◽  
Smita P. Soni ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Human Cell ◽  
Mammalian Cells ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Cell Plasma Membrane ◽  
Replication Process ◽  
Cell Plasma

ABSTRACTLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.IMPORTANCEThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

Optical measurement of the plasma-membrane potential of mammalian cells grown in monolayer culture

1981 ◽  
Vol 9 (1) ◽  
pp. 80-81 ◽  
Author(s):  
C. LINDSAY BASHFORD ◽  
KEITH A. FOSTER ◽  
KINGSLEY J. MICKLEM ◽  
CHARLES A. PASTERNAK
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Mammalian Cells ◽  
Monolayer Culture ◽  
Optical Measurement ◽  
Plasma Membrane Potential

scholarly journals Dependence of mammalian putrescine and spermidine transport on plasma-membrane potential: identification of an amiloride binding site on the putrescine carrier

1998 ◽  
Vol 330 (3) ◽  
pp. 1283-1291 ◽  
Author(s):  
Richard POULIN ◽  
Chenqi ZHAO ◽  
Savita VERMA ◽  
René CHAREST-GAUDREAULT ◽  
Marie AUDETTE
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Binding Site ◽  
Biochemical Properties ◽  
Mitochondrial Potential ◽  
Plasma Membrane Potential ◽  
High K ◽  
Polyamine Transport ◽  
Low K

The mechanism of mammalian polyamine transport is poorly understood. We have investigated the role of plasma-membrane potential (ΔΨpm) in putrescine and spermidine uptake in ZR-75-1 human breast cancer cells. The rate of [3H]putrescine and [3H]spermidine uptake was inversely correlated to extracellular [K+] ([K+]o) and to ΔΨpm, as determined by the accumulation of [3H]tetraphenylphosphonium bromide (TPP). Inward transport was unaffected by a selective decrease in mitochondrial potential (ΔΨmit) induced by valinomycin at low [K+]o, but was reduced by ≈ 60% by the rheogenic protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP), which rapidly (≤ 15 min) collapsed both ΔΨpm and ΔΨmit. Plasma-membrane depolarization by high [K+]o or CCCP did not enhance putrescine efflux in cells pre-loaded with [3H]putrescine, suggesting that decreased uptake caused by these agents did not result from a higher excretion rate. On the other hand, the electroneutral K+/H+ exchanger nigericin (10 μM) co-operatively depressed [3H]TPP, [3H]putrescine and [3H]spermidine uptake in the presence of ouabain. Suppression of putrescine uptake by nigericin+ouabain was Na+-dependent, suggesting that plasma-membrane repolarization by the electrogenic Na+ pump was required upon acidification induced by nigericin, due to the activation of the Na+/H+ antiporter. The sole addition of 5-N,N-hexamethylene amiloride, a potent inhibitor of the Na+/H+ antiporter, strongly inhibited putrescine uptake in a competitive fashion [Ki 4.0±0.9 (S.D.) μM], while being a weaker antagonist of spermidine uptake. The potency of a series of amiloride analogues to inhibit putrescine uptake was clearly different from that of the Na+/H+ antiporter, and resembled that noted for Na+ co-transport proteins. These data demonstrate that putrescine and spermidine influx is mainly unidirectional and strictly depends on ΔΨpm, but not ΔΨmit. This report also provides first evidence for a high-affinity amiloride-binding site on the putrescine carrier, which provides new insight into the biochemical properties of this transporter.

Role of Plasma Membrane Potential in Granulocyte Activation

1986 ◽  
Vol 488 (1 Membrane Path) ◽  
pp. 525-526
Author(s):  
FRANCESCO VIRGILIO ◽  
P. DANIEL LEW ◽  
TOMMY ANDERSSON ◽  
SUSAN TREVES ◽  
TULLIO POZZAN
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Plasma Membrane Potential

The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Kate Poole
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Mammalian Cells ◽  
Annual Review ◽  
Publication Date ◽  
Research Focus ◽  
Ionic Flux ◽  
Touch Sensation ◽  
Mechanical Sensing

Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation and hearing, recent data have highlighted the broad expression pattern of these molecules in mammalian cells. Disruption of mechanically activated channels has been shown to impact ( a) the development of mechanoresponsive structures, ( b) acute mechanical sensing, and ( c) mechanically driven homeostatic maintenance in multiple tissue types. The diversity of processes impacted by these molecules highlights the importance of mechanically activated ion channels in mammalian physiology. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals A novel mitochondrial Kv1.3–caveolin axis controls cell survival and apoptosis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jesusa Capera ◽  
Mireia Pérez-Verdaguer ◽  
Roberta Peruzzo ◽  
María Navarro-Pérez ◽  
Juan Martínez-Pinna ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Survival ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Membrane Microdomains ◽  
Functional Link ◽  
Caveolin 1 ◽  
Molecular Determinants ◽  
Apoptotic Effects

The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, at the plasma membrane or the mitochondria, could be responsible for such duality. While plasma membrane Kv1.3 facilitates proliferation, the mitochondrial channel modulates apoptotic signaling. Several molecular determinants of Kv1.3 drive the channel to the cell surface, but no information is available about its mitochondrial targeting. Caveolins, which are able to modulate cell survival, participate in the plasma membrane targeting of Kv1.3. The channel, via a caveolin-binding domain (CDB), associates with caveolin 1 (Cav1), which localizes Kv1.3 to lipid raft membrane microdomains. The aim of our study was to understand the role of such interactions not only for channel targeting but also for cell survival in mammalian cells. By using a caveolin association-deficient channel (Kv1.3 CDBless), we demonstrate here that while the Kv1.3–Cav1 interaction is responsible for the channel localization in the plasma membrane, a lack of such interaction accumulates Kv1.3 in the mitochondria. Kv1.3 CDBless severely affects mitochondrial physiology and cell survival, indicating that a functional link of Kv1.3 with Cav1 within the mitochondria modulates the pro-apoptotic effects of the channel. Therefore, the balance exerted by these two complementary mechanisms fine-tune the physiological role of Kv1.3 during cell survival or apoptosis. Our data highlight an unexpected role for the mitochondrial caveolin–Kv1.3 axis during cell survival and apoptosis.

scholarly journals Cortical Neurons Lacking KCC2 Expression Show Impaired Regulation of Intracellular Chloride

2005 ◽  
Vol 93 (3) ◽  
pp. 1557-1568 ◽  
Author(s):  
Lei Zhu ◽  
David Lovinger ◽  
Eric Delpire
Keyword(s):  
Plasma Membrane ◽  
Membrane Potential ◽  
Strong Evidence ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Reversal Potential ◽  
Excitable Cells ◽  
Low Concentrations ◽  
Pump Activity

As excitable cells, neurons experience constant changes in their membrane potential due to ion flux through plasma membrane channels. They maintain their transmembrane cation concentrations through robust Na+/K+-ATPase pump activity. During synaptic transmission and spread of action potentials, the concentration of the major anion, Cl−, is also under constant challenge from membrane potential changes. Moreover, intracellular Cl− is also affected by ligand-gated Cl− channels such as GABAA and glycine receptors. To regulate intracellular Cl− in an electrically silent manner, neurons couple the movement of Cl− with K+. In this study, we have used gene-targeted KCC2−/− mice to provide strong evidence that KCC2, the neuronal-specific K-Cl co-transporter, drives neuronal Cl− to low concentrations, shifting the GABA reversal potential toward more negative potentials, thus promoting hyperpolarizing GABA responses. Cortical neurons lacking KCC2, not only fail to show a developmental decrease in [Cl−]i, but also are unable to regulate [Cl−]i on Cl− loading or maintain [Cl]i during membrane depolarization. These data are consistent with the central role of KCC2 in promoting inhibition and preventing hyperexcitability.

Sign in / Sign up

Export Citation Format

Share Document