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Biomedical subjects

Mei Zhang

Publications and source records attributed to Mei Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2004

[A multi-center clinical trial of recombinant human thrombopoietin in chronic refractory idiopathic thrombocytopenic purpura].

OBJECTIVE: To evaluate the efficacy and safety of human recombinant thrombopoietin (rhTPO, a product of Sunshine Pharmaceutical Co Ltd, China) in chronic refractory idiopathic thrombocytopenic purpura. METHODS: Eighty-two patients with chronic refractory idiopathic purpura received daily subcutaneous administration of rhTPO at a dose of 1.0 micro g/kg for a maximum of 14 doses. RESULTS: After the beginning of treatment, the median platelet counts increased from 15.5 (6.0 - 24.0) x 10(9)/L to 27.5 (16.0-47.0) x 10(9)/L, 35.0 (20.5-78.0) x 10(9)/L and 77.0 (41.8-119.5) x 10(9)/L on the fifth, seventh and fifteenth day, respectively (P < 0.01). After the discontinuation of rhTPO administration, the platelet count decreased gradually. On the twenty-eighth day, the median platelet count was 76.5 (35-120.3) x 10(9)/L, which was still significantly higher than the level before the treatment (P < 0.01). The overall response rate was 85.3%. The rate in the group with remarkable response (platelet count > or = 100 x 10(9)/L without bleeding) was 58.5% and that in the good response group (platelet count > or = 50 x 10(9)/L or 30 x 10(9)/L higher than the count before the treatment, without bleeding) was 26.8%. Only 3 patients had mild clinical untoward reactions. Low titer (1:5) of anti-TPO antibody in serum was detected with ELISA in one of the sixteen patients who received the test on the twenty-first and twenty-eighth day. Neutralizing test using TPO-dependent cell line showed that the positive serum had no neutralizing activity on rhTPO. CONCLUSION: Consecutive subcutaneous injection of rhTPO for a maximum of 14 days was associated with a temporary elevation in platelet counts in patients with chronic refractory ITP with tolerable adverse effects.

Adult↗
PubMed2004

Establishing an animal model of unstable atherosclerotic plaques.

BACKGROUND: Atherosclerotic plaque rupture and coronary thrombosis are the main causes of acute coronary syndromes. However, there is no animal model of unstable atherosclerotic plaques. The presence of the p53 gene in advanced atherosclerotic plaques and the sensitivity to p53-induced apoptosis of smooth muscle cells isolated from these plaques prompted us to build an animal model of unstable atherosclerotic plaques using p53 gene transfer. METHODS: Sixty-four New Zealand white rabbits were randomly divided into two groups: group A (n=54) and group B (n=10). Rabbits in group A underwent balloon-induced abdominal aortic wall injury and were then given a diet of 1% cholesterol, while rabbits in group B were given a diet of 1% cholesterol without the induction of aortic wall injury. At the end of the eighth week, rabbits in group A were randomly divided into two subgroups: group A1 (n=27) and group A2 (n=27). Recombinant adenovirus carrying p53 or beta-galactosidase (LacZ) genes were injected through a catheter into the aortic segments rich in plaques in groups A1 and A2, respectively. Two weeks later, 10 rabbits each from groups A1 and A2 were killed to observe the occurrence of spontaneous plaque ruptures, and the remaining rabbits in groups A1, A2, and B all underwent pharmacological triggering with an injection of Chinese Russell's viper venom (CRVV) and histamine. RESULTS: The over expression of p53 in group A1 [(32.4 +/- 10.2)% vs (15.8 +/- 3.6)% in group A2 and (16.2 +/- 6.7)% in group B, P < 0.001, respectively] resulted in a marked increase in cellular apoptosis [(2.5 +/- 0.8)% vs (1.0 +/- 0.3)% in group A2 and (0.9 +/- 0.4)% in group B, P < 0.01, respectively], an accumulation of inflammatory cells within the plaques, and a significant decrease in vascular smooth muscle cells (VSMCs) and in the thickness of the fibrous caps. Although spontaneous plaque rupture was rare in group A1, plaque ruptures and thrombosis occurred in 12 rabbits with a total of 20 lesions after pharmacological triggering. By contrast, pharmacological triggering led to plaque rupture and thrombosis in only 5 rabbits for a total of 7 lesions in group A2 and in none of the rabbits in group B. CONCLUSION: After transfection with human wild-type p53 gene and pharmacological triggering, plaque rupture and thrombosis occur in most atherosclerotic lesions in rabbits, thus offering a reliable model for the further study of unstable atherosclerotic plaques.

Animals↗
PubMed2004

[Signal transduction on transdifferentiation of renal tubular epithelial cell].

It is an important cell biological phenomenon that epithelial cells transit into mesenchymal cells under special physiological and pathological condition. In recent years, it has been known that epithelial-mesenchymal-transition may be mediated by several intracellular signaling pathways, such as MAPK, Rho, Src, PI3 kinase and Smads. Renal tubular epithelial cells have been observed to transit to myo-fibroblasts in renal diseases. However, the intracellular signaling pathways are rarely known. The progress on this field is reviewed.

Animals↗
PubMed2003

Chain conformation of sulfated derivatives of beta-glucan from sclerotia of Pleurotus tuber-regium.

Six water-insoluble (1-->3)-beta-D-glucan fractions TM8-1 to TM8-6 with weight-average molecular mass Mw ranging from 5.76 to 77.4x10(4) obtained from the sclerotia of Pleurotus tuber-regium were sulfated to produce the water-soluble fractions S-TM8-1 to S-TM8-6 with Mw from 6.0 to 64.8x10(4). The degree of substitution (DS) of S-TM8 fractions was analyzed by elemental analysis (EA) to be 1.14-1.74. The 13C NMR results indicated that the C-6 was fully substituted, and C-2, C-4 were partially substituted by the sulfo-groups. The Mw and the intrinsic viscosity [eta] of the S-TM8 fractions were measured, respectively, by size-exclusion chromatography combined with laser light scattering (SEC-LLS), LLS and viscometry in phosphate buffer solution (PBS) at 37 degrees C. The dependences of [eta] and radius of gyration z(1/2) on Mw for the S-TM8 samples were found to be [eta]=1.89x10(-2) Mw(0.70) (cm3/g) and z(1/2)=1.12x10(-4) Mw(0.81) (nm) in the Mw range tested. Based on current theories for a wormlike chain model, the molar mass per unit contour length ML and persistence length q of the S-TM8 were calculated to be 990 nm(-1) and 8.5 nm, respectively. The relatively higher q value suggested a more expanded flexible chain of S-TM8 in PBS. The water-solubility and relatively expanded chain conformation of the STM8 fractions were considered to be significant to their antiviral activity.

Algorithms↗
PubMed2003

The cellular distribution and oxidation state of platinum(II) and platinum(IV) antitumour complexes in cancer cells.

The cellular distribution of platinum in A2780 ovarian cancer cells treated with cisplatin and platinum(IV) complexes with a range of reduction potentials has been examined using elemental analysis (synchrotron radiation-induced X-ray emission). The cellular distribution of platinum(IV) drugs after 24 h is similar to that of cisplatin, consistent with the majority of administered platinum(IV) drugs being reduced. Micro-X-ray absorption near-edge spectra of cells treated with cisplatin and platinum(IV) complexes confirmed the reduction of platinum(IV) to platinum(II). In cells treated, the most difficult to reduce complex, cis, trans, cis-[PtCl(2)(OH)(2)(NH(3))(2)], platinum(IV) was detected in the cells along with platinum(II). The observations are in accordance with the relative ease of reduction of the platinum(IV) complexes used and support the requirement of reduction for activation of platinum(IV) complexes.

Antineoplastic Agents↗
PubMed2003

[Interleukin-1beta-induced transdifferentiation of renal proximal tubular cells is mediated by p38 mitogen-activated protein kinase phosphorylation].

OBJECTIVE: To investigate the role of p38MAPK signaling pathway in interleukin (IL)-1beta induced transdifferentiation and its functional influences in human renal proximal tubular cell line HK-2 cells. METHODS: Human renal proximal tubular cells, cell line HK-2, were cultured and then co-incubated with IL-1beta (10 ng/ml) for 24 hours. The expression and distribution of cytokeratin and alpha-smooth muscle actin (SMA), markers of transdifferentiation of renal proximal tubular cells, were detected by immunofluorescence staining and confocal microscopy. Western blot technique was used to detect the expression of alpha-SMA 2, 4, 6, 12, 24, and 48 hours after IL-1beta stimulation. The morphology of cells was monitored from the 1st to the 5th day. Expression of alpha-SMA, phosphorylation of p38MAPK was assayed by western blot. Specific p38MAPK inhibitor SB203580 was added into the culture of HK-2 cells, 24 hours later IL-1beta was added for 24 hours Cell-cell adhesion and migration assay were performed. Inverted microscopy was used to examine the morphology of cells after stimulation of IL-1beta for 24 hours. Western blot technique was used to detected total and phosphorylated p38MAPK after stimulation of IL-1beta for 2, 5, 15, 30, 60 and 120 min. RESULTS: The phosphorylation of p38MAPK was increased after treatment of IL-1beta, and reached the level of 1.7 times the basic level 5 - 30 minutes after stimulation (P < 0.05). Almost no expression of alpha-SMA was shown in the control group. Two hours after IL-1beta stimulation, the expression of alpha-SMA was increased a little followed by an up-regulated expression of alpha-SMA 6 to 48 hours after the stimulation. The expression of alpha-SMA was down-regulated by 40% in the SB203580 group in comparison with that in the control (P < 0.01) and by 50% in comparison with that in the IL-1beta group (P < 0.001). The cell number was not significantly different between the IL-1beta group and control group (P > 0.05). A decreased expression of cytokeratin and disordered distribution of alpha-SMA were shown in the cells 24 hours after stimulation of IL-1beta. The morphology of cells remained unchanged 1 to 5 days after IL-1beta stimulation. The cell-cell adhesion was almost identical in the groups with IL-1beta and/or SB203580 no in comparison with that in the control group (P > 0.05). The migration ability of HK-2 cells was 2.2 times that in the control group in the IL-1beta group (P < 0.05) and decreased by 35% in the SB203580 group (P < 0.01). SB203580 uppercased the IL-1beta-induced expression of alpha-SMA and the enhancement of cell migration ability were suppressed by 51% (P < 0.05). CONCLUSION: IL-1beta induces transdifferentiation of renal proximal tubular cells characterized by alpha-SMA expression and enhanced ability of cell migration. These effects are mediated, at least in part, through the activation of p38 MAPK signaling pathway.

Actins↗
PubMed2003

Antitumor activities of heteropolysaccharides of Poria cocos mycelia from different strains and culture media.

Ten water-soluble heteropolysaccharide fractions were isolated from Poria cocos mycelia cultured from one wild and one cultivated strain in two identical culture media differing only in one component: either corn steep liquor or bran extract. The chemical compositions, including monosaccharide profile, protein content, and molecular mass M(w) of the mycelial polysaccharides were determined. Both the in vitro and in vivo antitumor activities of the heteropolysaccharides were evaluated and compared. The heteropolysaccharides from Poria cocos mycelia cultured with the wild strain in a medium containing corn steep liquor exhibited the highest antitumor activities against Sarcoma 180 in vivo.

Animals↗
PubMed2003

Cardiolipin is not required to maintain mitochondrial DNA stability or cell viability for Saccharomyces cerevisiae grown at elevated temperatures.

In eukaryotic cells, the phospholipid cardiolipin (CL) is primarily found in the inner mitochondrial membrane. Saccharomyces cerevisiae mutants, unable to synthesize CL because of a null allele of the CRD1 gene (encodes CL synthase), have been reported with different phenotypes. Some mutants, when grown on a nonfermentable carbon source at elevated temperatures, exhibit mitochondrial DNA instability, loss of viability, and significant defects in several functions that rely on the mitochondrial energy transducing system (ETS). These mutants also lack the immediate precursor to CL, phosphatidylglycerol (PG), when grown on glucose as a carbon source. Other mutants show reduced growth efficiency on a nonfermentable carbon source but much milder phenotypes associated with growth at elevated temperatures and increased levels of PG when grown on glucose. We present evidence that mitochondrial DNA instability, loss of viability, and defects in the ETS exhibited at elevated temperatures by some mutants are caused by the reduced expression of the PET56 gene in the presence of the his3 Delta 200 allele and not the lack of CL alone. We also found that PG is present and elevated in all crd1 Delta strains when grown on glucose. A supermolecular complex between complex III and complex IV of the mitochondrial ETS detected in wild type cells was missing in all of the above crd1 Delta cells. The level of components of the ETS was also reduced in crd1 Delta cells grown at elevated temperatures because of reduced gene expression and not reduced stability. These results suggest that all phenotypes reported for cells carrying the his3 Delta 200 allele and lacking CL should be re-evaluated.

Base Sequence↗
PubMed2003

Fractionation and characterization of a Polysaccharide from the sclerotia of Pleurotus tuber-regium by preparative size-exclusion chromatography.

A kind of regenerated cellulose gel (RCG) particles were treated by toluene to obtain particles with smaller mean pore size, then was mixed with the cellulose gel with pore size of 370 and 525 nm. A preparative size-exclusion chromatography (SEC) column (700 x 20 mm) packed with three gel particles was used to fractionate water-soluble polysaccharide (WEP) extracted from the sclerotia of Pleurotus tuber-regium by aqueous solution. The exclusion limit and fractionation range of the stationary phase of the preparative SEC were molecular mass 8 x 10(5) and 5 x 10(3) to 8 x 10(5), respectively. The calibration curve of the preparative SEC was represented as: log M=13.96-0.53 Ve. The WEP sample (weight-average molecular mass M(w)=2.2 x 10(4), polydispersity=2.4) was divided into three fractions with M(w) ranging from 1.4 x 10(4) to 3.4 x 10(4) by the preparative SEC column, and the fractions were characterized by gas chromatography GC, SEC combined with laser light scattering (SEC-LLS) and viscometry. The unfractionated WEP exhibited triple peaks due to different molecular mass, but each fraction exhibited single peak with the polydispersity of 1.1-1.8 in the SEC patterns. The results indicated that the preparative SEC was efficient for fractionation of polysaccharides having low molecular weight and for determination of their molecular mass.

Chemical Fractionation↗
PubMed2003

XANES determination of the platinum oxidation state distribution in cancer cells treated with platinum(IV) anticancer agents.

Here we describe the use of X-ray absorption near edge spectroscopy (XANES) to provide information about the relative proportions of platinum(II) and platinum(IV) complexes by analyzing the XANES edge height. The intracellular reduction of platinum(IV) complexes in cancer cells has been observed directly, and the proportion of reduction after 2 h was found to correlate with the reduction potentials of the complexes.

Antineoplastic Agents↗
PubMed2003

Stimulus-dependent deacylation of bacterial lipopolysaccharide by dendritic cells.

We describe here a previously unrecognized property of dendritic cells (DCs), the ability to deacylate the lipid A moiety of gram-negative bacterial LPSs. Both immature DCs of the XS52 cell line and bone marrow-derived DCs produce acyloxyacyl hydrolase, an enzyme that detoxifies LPS by selectively removing the secondary acyl chains from lipid A. Acyloxyacyl hydrolase expression decreased when DCs were incubated with IL-4, IL-1 beta, TNF alpha, and an agonistic CD40 antibody (maturation cocktail), and increased after treatment with LPS, CpG oligodeoxynucleotides, or a gram-positive bacterium (Micococcus luteus). Maturation cocktail treatment also diminished, whereas LPS treatment enhanced or maintained the cells' ability to kill Escherichia coli, deacylate LPS, and degrade bacterial protein. Enzymatic deacylation of LPS is an intrinsic, regulated mechanism by which DCs may modulate host responses to this potent bacterial agonist.

Acylation↗
PubMed2003

TCGAP, a multidomain Rho GTPase-activating protein involved in insulin-stimulated glucose transport.

Insulin stimulates glucose uptake in fat and muscle cells via the translocation of the GLUT4 glucose transporter from intracellular storage vesicles to the cell surface. The signaling pathways linking the insulin receptor to GLUT4 translocation in adipocytes involve activation of the Rho family GTPases TC10alpha and beta. We report here the identification of TCGAP, a potential effector for Rho family GTPases. TCGAP consists of N-terminal PX and SH3 domains, a central Rho GAP domain and multiple proline-rich regions in the C-terminus. TCGAP specifically interacts with cdc42 and TC10beta through its GAP domain. Although it has GAP activity in vitro, TCGAP is not active as a GAP in intact cells. TCGAP translocates to the plasma membrane in response to insulin in adipocytes. The N-terminal PX domain interacts specifically with phos phatidylinositol-(4,5)-bisphosphate. Overexpression of the full-length and C-terminal fragments of TCGAP inhibits insulin-stimulated glucose uptake and GLUT4 translocation. Thus, TCGAP may act as a downstream effector of TC10 in the regulation of insulin-stimulated glucose transport.

3T3 Cells↗
PubMed2003

[Relationship between regression of hypertensive left ventricular hypertrophy and improvement of coronary flow reserve].

OBJECTIVE: To elucidate the relationship between regression of hypertensive left ventricular hypertrophy (LVH) and changes of coronary flow reserve (CFR). METHODS: Ninety-six essential hypertensive patients with LVH were randomly divided into 3 groups: ramipril group, losartan group, and combination group. Before the treatment and 6 months after the treatment, left ventricular mass (LVM) was calculated by three-dimensional echocardiography and CFR was evaluated by transesophageal echocardiography with left anterior descending artery. CFR was calculated as the ratio of coronary flow velocity, after intravenous injection of dipyridamole (D), to rest peak velocity (R). All the indexes of the CFR were corrected by LVM. RESULTS: (1) The systolic blood pressure (SBP), diastolic blood pressure (DBP) and LVM were significantly decreased in ramipril group, losartan group and combination group after 6 months treatment (all P < 0.01). Diastolic flow velocity integral was used as one representative index of CFR. Compared with baseline values, the diastolic flow velocity intergral corrected by LVM (D/R DVi(C)) was significantly increased in ramipril group, losartan group and combination group (1.83 +/- 0.61 vs 1.57 +/- 0.58, P < 0.05; 1.94 +/- 0.45 vs 1.53 +/- 0.64, P < 0.01; 2.03 +/- 0.38 vs 1.49 +/- 0.34, P < 0.01). (3) The changes of D/R DVi(C) showed a positive correlation with the changes of LVM (r = 0.579, P < 0.05) and no significant correlation with the decrease of blood pressure (r = 0.288 and 0.295,both P > 0.05). CONCLUSION: Ramipril, losartan and combination of these two drugs all reduce blood pressure and LVH, and increases CFR. CFR corrected by LVM may help assess drug's effect on CFR. Improvement of CFR is associated with the regression of hypertensive LVH.

Adult↗
PubMed2003

Molecular mass and chain conformation of carboxymethylated derivatives of beta-glucan from sclerotia of Pleurotus tuber-regium.

Seven water-insoluble (1 --> 3)-beta-D-glucan fractions TM8-1 to TM8-7 with weight-average molecular mass M(w) ranged from 2.22 to 77.4 x 10(4) obtained from the sclerotia of Pleurotus tuber-regium were carboxymethylated to produce the water-soluble fractions CTM8-1 to CTM8-7 with M(w) ranged from 3.87 to 87.8 x 10(4). The degree of substitution (DS) of CTM8 fractions was analyzed by ir and elemental analysis (EA) to be 0.3-0.68. The M(w) and the intrinsic viscosity [eta] of the CTM8 fractions were measured by size-exclusion chromatography combined with multiangle laser light scattering (SEC-MALLS), MALLS, and viscometry in phosphate buffer solution (PBS) at 37 degrees C. The dependencies of [eta] and radius of gyration (z) (1/2) on M(w) for the CTM8 samples were found to be [eta] = (8.82 +/- 0.03) x 10(-3) M(w)(0.78 +/- 0.04) (cm(3) g(-1)) and (z) (1/2) = (3.09 +/- 0.05) x 10(-3) M(w)(0.75 +/- 0.06) (nm) in the M(w) range from 3.87 x 10(4) to 53.2 x 10(4). Based on current theories for wormlike chain model, the conformational parameters of the CTM8 were obtained to be 790 (nm(-1)) for M(L), 9.6 (nm) for q, which were higher than those of the native TM8 fractions, suggesting a more extended flexible chain of CTM8 in PBS. On the whole, the CTM8 fractions showed higher antitumor activity than their corresponding TM8 fractions. In view of data from molecular parameters and bioactivity, the antitumor activity of the CTM8 fractions may be correlated to its water solubility and relatively extended chain.

Carbohydrate Conformation↗
PubMed2003

BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but the mechanism of action with ErgTx1.

Peptide toxins with disulfide-stabilized structures have been used as molecular calipers to probe the outer vestibule structure of K channels. We want to apply this approach to the human ether-a-go-go-related gene (HERG) channel, whose outer vestibule is unique in structure and function among voltage-gated K channels. Our focus here is BeKm-1, a HERG-specific peptide toxin that can suppress HERG in the low nM concentration range. Although BeKm-1 shares the three-dimensional scaffold with the well-studied charybdotoxin, the two use different mechanisms in suppressing currents through their target K channels. BeKm-1 binds near, but not inside, the HERG pore, and it is possible that BeKm-1-bound HERG channels can conduct currents although with markedly altered voltage-dependence and kinetics of gating. BeKm-1 and ErgTx1 differ in three-dimensional scaffold, but the two share mechanism of action and have overlapping binding sites on the HERG channel. For both, residues in the middle of the S5-P linker (the putative 583-597 helix) and residues at the pore entrance are critical for binding, although specific contact points vary between the two. Toxin foot printing using BeKm-1 and ErgTx1 will likely provide complementary information about the unique outer vestibule structure of the HERG channel.

Amino Acid Sequence↗
PubMed2003

Transfer of metformin into human milk.

OBJECTIVES: Our objectives were to determine the milk-to-plasma ratio of metformin in lactating mothers and to estimate infant exposure. METHODS: Two studies were performed. In study 1, 3 nursing mothers taking metformin were studied throughout a dosing interval at steady state. Blood samples were obtained from 2 suckling infants. In study 2, 5 healthy lactating women who volunteered to express milk after weaning were given metformin, 500 mg, at weaning and were studied for up to 72 hours. In both studies, areas under the plasma and milk concentration-time curves were estimated, and the milk-to-plasma concentration ratio based on area under the concentration-time curve analysis was derived. The infant dose was calculated by standard methods. RESULTS: In study 1 the milk-to-plasma concentration ratios based on area under the concentration-time curve analysis were 0.37, 0.50, and 0.71. The estimated "doses" of metformin that would be ingested by the breast-fed infants were 0.18%, 0.20%, and 0.21% of the maternal doses, adjusted for weight. In the breast-fed infants, no metformin was detected (n = 2) or adverse effects noted (n = 3). In study 2, the milk-to-plasma concentration ratio based on area under the concentration-time curve analysis was unable to be calculated for 3 subjects because of the unexpected persistence of metformin in milk beyond the study period. For the 2 subjects studied for 72 hours, the milk-to-plasma concentration ratios based on area under the concentration-time curve analysis were 0.27 and 0.47 and the infant doses were 0.11% and 0.25%. The concentration-time profile for metformin in milk in all subjects was unexpectedly flat. CONCLUSIONS: Metformin appears to be "safe" during lactation because of low infant exposure. The unusual concentration-time profile for metformin in milk suggests that the transfer of metformin into milk is not solely dependent on passive diffusion.

Adult↗
PubMed2003

Negative charges in the transmembrane domains of the HERG K channel are involved in the activation- and deactivation-gating processes.

The transmembrane domains of HERG (S1-S3) contain six negative charges: three are conserved in all voltage-gated K channels (D456 and D466 in S2, D501 in S3) and three are unique to the EAG family (D411 in S1, D460 in S2, and D509 in S3). We infer the functional role of these aspartates by studying how substituting them with cysteine, one at a time, affects the channel function. D456C is not functional, suggesting that this negative charge may play a critical role in channel protein folding during biogenesis, as has been shown for its counterpart in the Shaker channel. Data from the other five functional mutants suggest that D411 can stabilize the HERG channel in the closed state, while D460 and D509 have the opposite effect. D466 and D501 both may contribute to voltage-sensing during the activation process. On the other hand, all five aspartates work in a concerted fashion in contributing to the slow deactivation process of the HERG channel. Accessibility tests of the introduced thiol groups to extracellular MTS reagents indicate that water-filled crevices penetrate deep into the HERG protein core, reaching the cytoplasmic halves of S1 and S2. At these deep locations, accessibility of 411C and 466C to the extracellular aqueous phase is voltage dependent, suggesting that conformational changes occur in S1 and S2 or the surrounding crevices during gating. Increasing extracellular [H+] accelerates HERG deactivation. This effect is suppressed by substituting the aspartates with cysteine, suggesting that protonation of these aspartates may contribute to the signaling pathway whereby external [H+] influences conformational changes in the channel's cytoplasmic domains (where deactivation takes place). There is no evidence for a metal ion binding site coordinated by negative charges in the transmembrane domains of HERG, as the one described for the EAG channel.

Amino Acid Sequence↗