scholarly journals Isoform‐specific effects of sialic acid on voltage‐dependent Na + channel gating: functional sialic acids are localized to the S5‐S6 loop of domain I

2002 ◽  
Vol 538 (3) ◽  
pp. 675-690 ◽  
Author(s):  
Eric S. Bennett
Keyword(s):  
Sialic Acid ◽  
Channel Gating ◽  
Sialic Acids ◽  
Na Channel ◽  
Specific Effects ◽  
Voltage Dependent ◽  
Domain I

scholarly journals Differential Sialylation Modulates Voltage-gated Na+ Channel Gating throughout the Developing Myocardium

2006 ◽  
Vol 127 (3) ◽  
pp. 253-265 ◽  
Author(s):  
Patrick J. Stocker ◽  
Eric S. Bennett
Keyword(s):  
Sialic Acid ◽  
Sodium Channel ◽  
Channel Gating ◽  
Sialic Acids ◽  
Na Channel ◽  
Voltage Gated Sodium Channel ◽  
Α Subunit ◽  
Rat Cardiomyocytes ◽  
Voltage Gated ◽  
Α Subunits

Voltage-gated sodium channel function from neonatal and adult rat cardiomyocytes was measured and compared. Channels from neonatal ventricles required an ∼10 mV greater depolarization for voltage-dependent gating events than did channels from neonatal atria and adult atria and ventricles. We questioned whether such gating shifts were due to developmental and/or chamber-dependent changes in channel-associated functional sialic acids. Thus, all gating characteristics for channels from neonatal atria and adult atria and ventricles shifted significantly to more depolarized potentials after removal of surface sialic acids. Desialylation of channels from neonatal ventricles did not affect channel gating. After removal of the complete surface N-glycosylation structures, gating of channels from neonatal atria and adult atria and ventricles shifted to depolarized potentials nearly identical to those measured for channels from neonatal ventricles. Gating of channels from neonatal ventricles were unaffected by such deglycosylation. Immunoblot gel shift analyses indicated that voltage-gated sodium channel α subunits from neonatal atria and adult atria and ventricles are more heavily sialylated than α subunits from neonatal ventricles. The data are consistent with approximately 15 more sialic acid residues attached to each α subunit from neonatal atria and adult atria and ventricles. The data indicate that differential sialylation of myocyte voltage-gated sodium channel α subunits is responsible for much of the developmental and chamber-specific remodeling of channel gating observed here. Further, cardiac excitability is likely impacted by these sialic acid–dependent gating effects, such as modulation of the rate of recovery from inactivation. A novel mechanism is described by which cardiac voltage-gated sodium channel gating and subsequently cardiac rhythms are modulated by changes in channel-associated sialic acids.

scholarly journals Molecular Action of Lidocaine on the Voltage Sensors of Sodium Channels

2003 ◽  
Vol 121 (2) ◽  
pp. 163-175 ◽  
Author(s):  
Michael F. Sheets ◽  
Dorothy A. Hanck
Keyword(s):  
Channel Gating ◽  
Ionic Current ◽  
Na Channel ◽  
Relative Reduction ◽  
Charge Movement ◽  
Charge Voltage ◽  
Voltage Sensors ◽  
Gating Charge ◽  
Voltage Dependent ◽  
Domain Iii

Block of sodium ionic current by lidocaine is associated with alteration of the gating charge-voltage (Q-V) relationship characterized by a 38% reduction in maximal gating charge (Qmax) and by the appearance of additional gating charge at negative test potentials. We investigated the molecular basis of the lidocaine-induced reduction in cardiac Na channel–gating charge by sequentially neutralizing basic residues in each of the voltage sensors (S4 segments) in the four domains of the human heart Na channel (hH1a). By determining the relative reduction in the Qmax of each mutant channel modified by lidocaine we identified those S4 segments that contributed to a reduction in gating charge. No interaction of lidocaine was found with the voltage sensors in domains I or II. The largest inhibition of charge movement was found for the S4 of domain III consistent with lidocaine completely inhibiting its movement. Protection experiments with intracellular MTSET (a charged sulfhydryl reagent) in a Na channel with the fourth outermost arginine in the S4 of domain III mutated to a cysteine demonstrated that lidocaine stabilized the S4 in domain III in a depolarized configuration. Lidocaine also partially inhibited movement of the S4 in domain IV, but lidocaine's most dramatic effect was to alter the voltage-dependent charge movement of the S4 in domain IV such that it accounted for the appearance of additional gating charge at potentials near −100 mV. These findings suggest that lidocaine's actions on Na channel gating charge result from allosteric coupling of the binding site(s) of lidocaine to the voltage sensors formed by the S4 segments in domains III and IV.

scholarly journals Contribution of Sialic Acid to the Voltage Dependence of Sodium Channel Gating

1997 ◽  
Vol 109 (3) ◽  
pp. 327-343 ◽  
Author(s):  
Eric Bennett ◽  
Mary S. Urcan ◽  
Sally S. Tinkle ◽  
Adam G. Koszowski ◽  
Simon R. Levinson
Keyword(s):  
Steady State ◽  
Sialic Acid ◽  
Voltage Dependence ◽  
Channel Gating ◽  
Chinese Hamster ◽  
Glycosylation Sites ◽  
Voltage Dependent ◽  
Negative Surface ◽  
Electrostatic Mechanism ◽  
External Calcium

A potential role for sialic acid in the voltage-dependent gating of rat skeletal muscle sodium channels (rSkM1) was investigated using Chinese hamster ovary (CHO) cells stably transfected with rSkM1. Changes in the voltage dependence of channel gating were observed after enzymatic (neuraminidase) removal of sialic acid from cells expressing rSkM1 and through the expression of rSkM1 in a sialylation-deficient cell line (lec2). The steady-state half-activation voltages (Va) of channels under each condition of reduced sialylation were ∼10 mV more depolarized than control channels. The voltage dependence of the time constants of channel activation and inactivation were also shifted in the same direction and by a similar magnitude. In addition, recombinant deletion of likely glycosylation sites from the rSkM1 sequence resulted in mutant channels that gated at voltages up to 10 mV more positive than wild-type channels. Thus three independent means of reducing channel sialylation show very similar effects on the voltage dependence of channel gating. Finally, steady-state activation voltages for channels subjected to reduced sialylation conditions were much less sensitive to the effects of external calcium than those measured under control conditions, indicating that sialic acid directly contributes to the negative surface potential. These results are consistent with an electrostatic mechanism by which external, negatively charged sialic acid residues on rSkM1 alter the electric field sensed by channel gating elements.

scholarly journals Unique Bell-shaped Voltage-dependent Modulation of Na+Channel Gating by Novel Insect-selective Toxins from the SpiderAgelena orientalis

2010 ◽  
Vol 285 (24) ◽  
pp. 18545-18554 ◽  
Author(s):  
Bert Billen ◽  
Alexander Vassilevski ◽  
Anton Nikolsky ◽  
Sarah Debaveye ◽  
Jan Tytgat ◽  
...  
Keyword(s):  
Channel Gating ◽  
Na Channel ◽  
Voltage Dependent

COMPARATIVE ACTION OF VARIOUS OESTROGENIC COMPOUNDS ON MOUSE VAGINAL SIALIC ACIDS (II)

1969 ◽  
Vol 62 (4) ◽  
pp. 663-670 ◽  
Author(s):  
Lars Carlborg
Keyword(s):  
Sialic Acid ◽  
Response Curve ◽  
Sialic Acids ◽  
Clear Cut ◽  
Suitable Parameter ◽  
Sufficient Degree ◽  
Comparative Action ◽  
Relative Potencies ◽  
Good Agreement

ABSTRACT Oestrogens administered in lower doses than necessary to induce full cornification of the mouse vagina induce mucification. It was shown previously that the degree of mucification could be estimated by quantitative determination of sialic acids. A suitable parameter for oestrogen assay was the measurement of vaginal sialic acid concentration which exhibited a clear cut dose response curve. Eleven assays of various oestrogens were performed with this method. Their estimated relative potencies were in good agreement with other routine oestrogen assays. A statistically sufficient degree of precision was found. The sensitivity was of the same order, or slightly higher, than the Allen-Doisy test.

Interspecific variation of zona pellucida glycoconjugates in several species of marsupial

Reproduction ◽  
2000 ◽  
pp. 111-120 ◽  
Author(s):  
JA Chapman ◽  
OW Wiebkin ◽  
WG Breed
Keyword(s):  
Glycine Max ◽  
Sialic Acid ◽  
Zona Pellucida ◽  
Fluorescein Isothiocyanate ◽  
Interspecific Variation ◽  
Lectin Histochemistry ◽  
Sialic Acids ◽  
Arachis Hypogea ◽  
Marsupial Species ◽  
Similar Intensity

The zona pellucida glycoconjugate content of several marsupial species was investigated using differential lectin histochemistry. Ovaries from fat-tailed dunnarts, a southern brown bandicoot, grey short-tailed opossums, brushtail possums, ringtail possums, koalas and eastern grey kangaroos were fixed, embedded in paraffin wax, sectioned and stained with ten fluorescein isothiocyanate-conjugated lectins. Sections were also incubated with either neuraminidase or saponified, respectively, before incubation with the lectins to identify saccharide residues masked by sialic acids or O-acetyl groups on sialic acids. The zonae pellucidae surrounding the oocytes of the marsupials demonstrated interspecific variation in glycoconjugate content, with mannose-containing glycoconjugates exhibiting the greatest variation. Some of the zona pellucida glycoconjugates of all species, except those of the opossums, were masked by sialic acid with an increase in fluorescence with lectins from Arachis hypogea (PNA), and Glycine max (SBA), after desialylation. The disaccharide beta-galactose(1-4)N-acetyl-D-glucosamine appeared to be conformationally masked by O-acetyl groups of sialic acids in the zonae pellucidae of all species, with an increase in fluorescence with the lectin from Erythrina cristagalli (ECA), after saponification. Similar intensity and localization of beta-(1-4)-N-acetyl-D-glucosamine, as shown by staining of the lectin from Triticum vulgaris (WGA), to the inner and outer regions of the zona pellucida, were found to those reported in eutherian species. WGA fluorescence became uniform throughout the zonae pellucidae after saponification, indicating differential O-acetylation of sialic acids on the internal compartment of the zonae pellucidae.

scholarly journals Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces

2021 ◽  
Author(s):  
Yixuan Xie ◽  
Siyu Chen ◽  
Qiongyu Li ◽  
Ying Sheng ◽  
Michael R Alvarez ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sialic Acid ◽  
Membrane Proteins ◽  
Cell Membranes ◽  
Sialic Acids ◽  
Cross Linking ◽  
Protein Networks ◽  
Cell Surfaces ◽  
Protein Cross Linking

A cross-linking method is developed to elucidate the glycan-mediated interactions between membrane proteins through sialic acids. The method provides previously unknown extensive glycomic interactions on cell membranes. The vast majority...

scholarly journals Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment

2017 ◽  
Vol 8 (9) ◽  
pp. 6165-6170 ◽  
Author(s):  
A. Matsumoto ◽  
A. J. Stephenson-Brown ◽  
T. Khan ◽  
T. Miyazawa ◽  
H. Cabral ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Boronic Acids ◽  
Sialic Acids ◽  
Strong Interactions ◽  
Acidic Ph ◽  
Acidic Environment ◽  
Selective Binding ◽  
High Affinity ◽  
Ph Conditions ◽  
Hypoxic Tumor

A group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids are described, with strong interactions under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment.

scholarly journals Automated solid-phase synthesis of oligosaccharides containing sialic acids

2015 ◽  
Vol 11 ◽  
pp. 617-621 ◽  
Author(s):  
Chian-Hui Lai ◽  
Heung Sik Hahm ◽  
Chien-Fu Liang ◽  
Peter H Seeberger
Keyword(s):  
Sialic Acid ◽  
Building Block ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Sialic Acids ◽  
Phase Synthesis ◽  
Glycosyl Phosphate

A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare α-sialylated oligosaccharides by automated solid-phase synthesis selectively.

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