scholarly journals Regulation of Connexin Hemichannels by Monovalent Cations

2005 ◽  
Vol 127 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Miduturu Srinivas ◽  
D. Paola Calderon ◽  
Jack Kronengold ◽  
Vytas K. Verselis
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Divalent Cations ◽  
Signaling Molecules ◽  
Primary Effect ◽  
Monovalent Cations ◽  
Modest Increase ◽  
Monovalent Ions ◽  
The Difference ◽  
Connexin Hemichannels

Opening of connexin hemichannels in the plasma membrane is highly regulated. Generally, depolarization and reduced extracellular Ca2+ promote hemichannel opening. Here we show that hemichannels formed of Cx50, a principal lens connexin, exhibit a novel form of regulation characterized by extraordinary sensitivity to extracellular monovalent cations. Replacement of extracellular Na+ with K+, while maintaining extracellular Ca2+ constant, resulted in >10-fold potentiation of Cx50 hemichannel currents, which reversed upon returning to Na+. External Cs+, Rb+, NH4+, but not Li+, choline, or TEA, exhibited a similar effect. The magnitude of potentiation of Cx50 hemichannel currents depended on the concentration of extracellular Ca2+, progressively decreasing as external Ca2+ was reduced. The primary effect of K+ appears to be a reduction in the ability of Ca2+, as well as other divalent cations, to close Cx50 hemichannels. Cx46 hemichannels exhibited a modest increase upon substituting Na+ with K+. Analyses of reciprocal chimeric hemichannels that swap NH2- and COOH-terminal halves of Cx46 and Cx50 demonstrate that the difference in regulation by monovalent ions in these connexins resides in the NH2-terminal half. Connexin hemichannels have been implicated in physiological roles, e.g., release of ATP and NAD+ and in pathological roles, e.g., cell death through loss or entry of ions and signaling molecules. Our results demonstrate a new, robust means of regulating hemichannels through a combination of extracellular monovalent and divalent cations, principally Na+, K+, and Ca2+.

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

scholarly journals Mechanisms Underlying Connexin Hemichannel Activation in Disease

2021 ◽  
Vol 22 (7) ◽  
pp. 3503
Author(s):  
Raf Van Campenhout ◽  
Ana Rita Gomes ◽  
Timo W.M. De Groof ◽  
Serge Muyldermans ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Cell Death ◽  
Gap Junctions ◽  
Connexin Hemichannel ◽  
Extracellular Environment ◽  
Connexin Hemichannels

Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.

scholarly journals Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarely C. Hoffiz ◽  
Alexandra Castillo-Ruiz ◽  
Megan A. L. Hall ◽  
Taylor A. Hite ◽  
Jennifer M. Gray ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Surrogate Marker ◽  
Plasma Osmolality ◽  
Neuronal Cell ◽  
Clinical Findings ◽  
Neural Activation ◽  
Vasopressin Release ◽  
Neuroendocrine Response ◽  
The Difference

AbstractLong-standing clinical findings report a dramatic surge of vasopressin in umbilical cord blood of the human neonate, but the neural underpinnings and function(s) of this phenomenon remain obscure. We studied neural activation in perinatal mice and rats, and found that birth triggers activation of the suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus. This was seen whether mice were born vaginally or via Cesarean section (C-section), and when birth timing was experimentally manipulated. Neuronal phenotyping showed that the activated neurons were predominantly vasopressinergic, and vasopressin mRNA increased fivefold in the hypothalamus during the 2–3 days before birth. Copeptin, a surrogate marker of vasopressin, was elevated 30-to 50-fold in plasma of perinatal mice, with higher levels after a vaginal than a C-section birth. We also found an acute decrease in plasma osmolality after a vaginal, but not C-section birth, suggesting that the difference in vasopressin release between birth modes is functionally meaningful. When vasopressin was administered centrally to newborns, we found an ~ 50% reduction in neuronal cell death in specific brain areas. Collectively, our results identify a conserved neuroendocrine response to birth that is sensitive to birth mode, and influences peripheral physiology and neurodevelopment.

scholarly journals An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death

2015 ◽  
Vol 290 (34) ◽  
pp. 20841-20855 ◽  
Author(s):  
Mercè Garcia-Belinchón ◽  
María Sánchez-Osuna ◽  
Laura Martínez-Escardó ◽  
Carla Granados-Colomina ◽  
Sònia Pascual-Guiral ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Chromatin Condensation ◽  
Biochemical Network ◽  
Display Type ◽  
Nuclear Morphology ◽  
Type Ii ◽  
Caspase Activation ◽  
Membrane Leakage ◽  
Nuclear Alterations

Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as “apoptosis-necrosis continuum.” To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death.

Mechanism of human sperm activation by extracellular ATP

1996 ◽  
Vol 270 (6) ◽  
pp. C1709-C1714 ◽  
Author(s):  
C. Foresta ◽  
M. Rossato ◽  
P. Chiozzi ◽  
F. Di Virgilio
Keyword(s):  
Plasma Membrane ◽  
Acrosome Reaction ◽  
Human Sperm ◽  
Extracellular Atp ◽  
Effective Concentration ◽  
Na Channel ◽  
Monovalent Cations ◽  
Sperm Activation ◽  
Gated Channel ◽  
Sperm Plasma Membrane

We have identified the mechanism whereby extracellular ATP (ATPe) triggers the acrosome reaction in human spermatozoa. This nucleotide opens a ligand-gated ion channel expressed on the sperm plasma membrane. ATPe threshold and 50% effective concentration calculated on the total added ATPe are 0.1 and 2 mM, respectively, corresponding to a free ATP concentration (ATP4-) of 3 and 200 microM, respectively. The ATPe-gated channel is selective for monovalent cations (Na+, choline, and methylglucamine), whereas on the contrary, permeability to Ca2+ is negligible. Isosmolar replacement of extracellular Na+ with sucrose fully blocked ATPe-dependent sperm activation, thus suggesting a mandatory role for Na+ influx. These results show that human sperm express an ATPe-gated Na+ channel that might have an important role in sperm activation before egg fertilization.

Cation exchange in cell walls of gram-positive bacteria

1976 ◽  
Vol 22 (7) ◽  
pp. 975-982 ◽  
Author(s):  
Robert E. Marquis ◽  
Kathleen Mayzel ◽  
Edwin L. Carstensen
Keyword(s):  
Cation Exchange ◽  
Cell Walls ◽  
Divalent Cations ◽  
Teichoic Acid ◽  
Dry Weight ◽  
High Ionic Strength ◽  
Monovalent Cations ◽  
Anionic Sites ◽  
Gram Positive Bacteria ◽  
Anionic Groups

The relative affinities of various cations for anionic sites in isolated, bacterial cell walls were assessed by means of a technique involving displacement of one cation by another. The affinity series determined was [Formula: see text]. High affinity was correlated with low mobility of the bound ions in an electric field. The net cation-exchange capacities of walls isolated from a variety of bacteria were estimated by preparing the magnesium forms of the walls, washing them well with deionized water to remove supernumerary ions, and then completely displacing the magnesium with Na+ or H+. Total amounts of magnesium displaced varied from 73 μmol per gram dry weight, for walls of the teichoic acid-deficient 52A5 strain of Staphylococcus aureus to about 520 μmol per gram for Bacillus megaterium KM walls. The amount of displacable magnesium was inversely related to the physical compactness of the walls, except for walls of Streptococcus mutans GS-5. It was found that magnesium or calcium ions can each neutralize, or pair with, two anionic groups in walls suspended in ion-deficient media. Previous work had indicated that these ions may pair with only one anionic group at high ionic strength. Therefore, it appeared that there is a great deal of flexibility in the arrangement of charged groups in the wall. It was concluded also that for cells growing in commonly used laboratory media, which generally contain large excesses of monovalent versus divalent cations, there is a mix of small, cationic counterions in the wall and that monovalent cations may predominate even though the wall has higher affinity for divalent ions.

scholarly journals Cation-chloride cotransporters, Na/K pump, and channels in cell water and ions regulation: in silico and experimental studies of the U937 cells under stopping the pump and during RVD

2021 ◽  
Author(s):  
Alexey A Vereninov ◽  
Valentina Yurinskaya
Keyword(s):  
Plasma Membrane ◽  
Cell Membrane ◽  
Real Time ◽  
Intracellular Signaling ◽  
Ion Homeostasis ◽  
Regulatory Volume Decrease ◽  
Experimental Studies ◽  
U937 Cells ◽  
Ionic Homeostasis ◽  
Monovalent Ions

Cation-coupled chloride cotransporters play a key role in generating the Cl− electrochemical gradient on the cell membrane which is important for regulation of many cellular processes. However, the cooperation of transporters and channels of the plasma membrane in holding the ionic homeostasis of the whole cell remains poorly characterized because of the lack of a suitable tool for its computation. Our software successfully predicted in real-time changes in the ion homeostasis of U937 cells after stopping the Na/K pump, but so far considered the model with only NC cotransporter. Here the model with all main types of cotransporters is used in computation of the rearrangements of ionic homeostasis due to stopping the pump and associated with the regulatory volume decrease (RVD) of cells swollen in hypoosmolar medium. The parameters obtained for the real U937 cells are used. Successful prediction of changes in ion homeostasis in real-time after stopping the pump using the model with all major cotransporters indicates that the model is reliable. Using this model for analysis RVD showed that there is a "physical" RVD, associated with the time-dependent changes in electrochemical ion gradients, but not with alteration of channels and transporters of the plasma membrane that should be considered in studies of truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the partial unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.

scholarly journals Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1354-1361 ◽  
Author(s):  
JR O'Brien ◽  
GP Salmon
Keyword(s):  
Shear Stress ◽  
Bleeding Time ◽  
Platelet Rich Plasma ◽  
Divalent Cations ◽  
Mean Transit Time ◽  
Platelet Glycoprotein ◽  
High Shear ◽  
The Difference ◽  
Von Willebrand’S Factor ◽  
Induced Aggregation

The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of “membrane-active” drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin- induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.

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