Search PubMed⌕ Search

Biomedical subjects

S Yan

Publications and source records attributed to S Yan.

At least 55 records · Page 3Linked to original sources

[A preliminary report of cleft palate repair by rotation and advancement of full thickness soft palate].

OBJECTIVE: To introduce a new method of functional cleft palate repair. METHODS: Square flap A and triangular flaps B, C, D were designed on the each sides of defect at soft palate. They were advanced and rotated, each flap was inserted to the opposite side and then sutured. The lavator veli (LV) muscle was detached and sutured to reconstruct the steady LV muscle sling. RESULTS: This method was applied in 37 cases with satisfactory results of extending the soft palate, forming the dynamic soft palate muscular sling, and achieving velopharyngeal closure (VPC) 31 cases were flowed-up for half year to 2 years, the effects of operation are stable. CONCLUSIONS: This method not only close the cleft but also restore the soft palate's function of elevating and pushing back to achieve the ideal VPC.

Adolescent↗

Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is due to a lack of interactions with the center of the peptide.

Class I major histocompatibility complex (MHC) molecules bind short peptides derived from proteins synthesized within the cell. These complexes of peptide and class I MHC (pMHC) are transported from the endoplasmic reticulum to the cell surface. If a clonotypic T cell receptor expressed on a circulating T cell binds to the pMHC complex, the cell presenting the pMHC is killed. In this manner, some tumor cells expressing aberrant proteins are recognized and removed by the immune system. However, not all tumors are recognized efficiently. One reason hypothesized for poor T cell recognition of tumor-associated peptides is poor binding of those peptides to class I MHC molecules. Many peptides, derived from the proto-oncogene HER-2/neu have been shown to be recognized by cytotoxic T cells derived from HLA-A2(+) patients with breast cancer and other adenocarcinomas. Seven of these peptides were found to bind with intermediate to poor affinity. In particular, GP2 (HER-2/neu residues 654-662) binds very poorly even though it is predicted to bind well based upon the presence of the correct HLA-A2.1 peptide-binding motif. Altering the anchor residues to those most favored by HLA-A2.1 did not significantly improve binding affinity. The crystallographic structure shows that unlike other class I-peptide structures, the center of the peptide does not assume one specific conformation and does not make stabilizing contacts with the peptide-binding cleft.

Amino Acid Sequence↗

The Leishmania donovani LD1 locus gene ORFG encodes a biopterin transporter (BT1).

We have previously described two genes, ORFF and ORFG, from the LD1 locus near one telomere of chromosome 35, which are frequently amplified in Leishmania isolates. In Leishmania donovani LSB-51.1, gene conversion of the rRNA gene locus on chromosome 27 with these two genes resulted in their over-expression, because of their transcription by the RNA polymerase I-mediated rRNA promoter. The predicted ORFG protein has substantial sequence homology to the ESAG10 gene product from the Trypanosoma brucei VSG expression site and both are putative membrane proteins. Using successive rounds of gene replacement of the three ORFG genes in L. donovani LSB-51.1, ORFG null mutants were obtained. These mutant cell lines show a direct relationship between ORFG mRNA, protein expression levels and active transport of biopterin into the cells. Transformation of the null mutant with a plasmid containing ORFG restores biopterin transport activity. In addition, the null mutants are unable to grow in the absence of supplemental biopterin. Thus, ORFG encodes a biopterin transporter and has been renamed BTI.

Animals↗

Characterization of the Leishmania donovani ribosomal RNA promoter.

The rRNA genes of Leishmania donovani are organized on chromosome 27 as tandem repeats of approximately 12.5-kb units that each contain a promoter, the subunit rRNAs, and approximately 39 copies of a 64-bp species-specific sequence. The transcription initiation site was mapped to 1020 bp upstream of the 18S rRNA gene by RNase protection and primer extension. A 349-bp sequence between the 64-bp repeats and the 18S rRNA gene appears to contain a promoter, since it directs a 60-fold increase in luciferase expression over the no-insert control in transient transfection assays. Stepwise deletion and 10-bp replacement studies identified three domains that affect promoter activity. In strain LSB-51.1, a naturally occurring gene conversion with a portion of the LD1 sequence from chromosome 35 replaced the rRNA genes within one repeat unit, from downstream of the promoter to within the 64-bp repeats. Northern blot analysis of RNA from LSB-51.1 showed large transcripts from the external spacer regions that are not normally transcribed. These results imply that the gene conversion eliminated sequences at or near the 5' terminus of the 64-bp repeats which normally function in transcription termination.

Animals↗

The inwardly rectifying K(+) channel subunit GIRK1 rescues the GIRK2 weaver phenotype.

The weaver (wv) gene has been identified as a glycine to serine substitution at residue 156 in the H5 region of inwardly rectifying K(+) channel, GIRK2. The mutation is permissive for the expression of homotetrameric channels that are nonselective for cations and G-protein-independent. Coexpression of GIRK2wv with GIRK1, GIRK2, or GIRK3 in Xenopus oocytes along with expression of subunit combinations linked as dimers and tetramers was used to investigate the effects of the pore mutation on channel selectivity and gating as a function of relative subunit position and number within a heterotetrameric complex. GIRK1 formed functional, K(+) selective channels with GIRK2 and GIRK3. Coexpression of GIRK2wv with GIRK1 gave rise to a component of K(+)-selective, G-protein-dependent current. Currents resulting from coexpression of GIRK2wv with GIRK2 or GIRK3 were weaver-like. Current from dimers of GIRK1-GIRK2wv, GIRK2-GIRK2wv, and GIRK3-GIRK2wv was phenotypically similar to that obtained from coexpression of monomers. Linked tetramers containing GIRK1 and GIRK2wv in an alternating array gave rise to wild-type, K(+)-selective currents. When two mutant subunits were arranged adjacently in a tetramer, currents were weaver-like. These results support the hypothesis that in specific channel stoichiometries, GIRK1 rescues the weaver phenotype and suggests a basis for the selective neuronal vulnerability that is observed in the weaver mouse.

Amino Acid Substitution↗

Differentiating agents regulate cathepsin B gene expression in HL-60 cells.

We utilized HL-60 cells as a model system to examine the regulation of ctsb gene expression by differentiating agents. Inducers of monocytic differentiation [phorbol ester (PMA), calcitriol (D3), and sodium butyrate (NaB)] and inducers of granulocytic differentiation [all-trans retinoic acid (RA) and 9-cis retinoic acid (9-cis RA)] increase ctsb mRNA levels in a dose-dependent manner as determined by Northern blot hybridization. D3 and retinoids exert additive effects, suggesting that these agents act in part through distinct pathways. Actinomycin D decay experiments indicate that D3, NaB, RA, and 9-cis RA do not alter mRNA stability. In contrast, PMA markedly increases the half-life of ctsb mRNA. In transient transfection assays, PMA and NaB both stimulate transcription of the luciferase reporter gene placed under the control of ctsb promoter fragments. Thus, inducers of HL-60 cell differentiation can regulate the expression of the ctsb gene at both transcriptional and posttranscriptional levels.

Alitretinoin↗

Differential expression of RAB5A in human lung adenocarcinoma cells with different metastasis potential.

For the sake of better understanding the molecular mechanism of neoplasia, we have used the mRNA differential display technique to analyze two human lung adenocarcinoma cell lines, AGZY83-a and Anip973. Anip973 was isolated from AGZY83-a, but manifested much higher metastatic potential than the parent line. We found that a significant differential cDNA fragment in Anip973 was over-expressed, then over-expressed cDNA fragment was cloned and sequenced. It showed that the over-expressed cDNA in Anip973 was RAB5A cDNA. And the RAB5A cDNA sequence was corresponding between the two cells. To determine whether RAB5A may be differentially expressed in the two human lung adenocarcinoma cells at protein level, we further detected RAB5A protein in the two cells by using immunofluorescent method. RAB5A protein was upregulated in highly metastatic Anip973. We also detected the difference in RAB5A gene expression at RNA level in human non-small cell lung carcinoma by RT-PCR. Using immunohistochemical staining, we also examined RAB5A change at protein level in 45 cases human non-small cell lung carcinoma paraffin sections. The results proved the evidence of upregulation of RAB5A in malignant tumor, indicated over-expression of RAB5A gene was correlated with the malignant degree and metastatic potential of lung cancer(chi2 test, p < 0.01). The RAB5A gene is a member of RAS superfamily, which can transcribe GTP-binding protein that plays an important role in signal transduction of protein trafficking at the cell surface and GDP/GTP cycle in the regulation of endocytotic membrane traffic. Thus our results indicated that overexpression of the RAB5A gene was involved in the process of transformation from AGZY83-a to the higher metastatic cell line Anip973. The result may be a powerful experimental evidence that over-expression of RAB5A gene associated with neoplasia metastasis.

Adenocarcinoma↗

Essential drugs for cancer therapy: a World Health Organization consultation.

The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible.

Antineoplastic Agents↗

Contribution of late professor T. C. Tung to the experimental embryology of Amphioxus. In memory of the 20th anniversary of Professor T. C. Tung's death.

Professor T. C. Tung (Fig. 1) was a prominent experimental embryologist in China. He was born in Jin County, Zhejiang Province, China in 1902. After he obtained his Bachelor's degree from the Department of Biology, Fudan University, Shanghai in 1927, he was appointed as a teaching assistant in that department until he moved to Belgium in 1930. He studied as a graduate student in Professors A. Brachet and A. M. Dalcq's laboratory at the Universite Libre de Bruxelles, Belgium and obtained his Doctor of Science degree there in 1934. During that period, he made two short working visits to the Institute of Marine Biology in France and took one training course at Cambridge University (UK). In 1934, he was invited to return to China as a Full Professor to teach at several Chinese universities, (Shandong University in Qingdao, Shandong Province; the National University in Nanjing; and Fudan University in Shanghai). He spent 1 year at Yale University (USA) between 1948 and 1949 as an invited scientist in a joint research project and finally returned to China in 1949. He was Chairman of the Department of Zoology, Shandong University in Qingdao (1949-1952), Vice-President of Shandong University (1952-1960), Director of the Marine Biological Institute, the Chinese Academy of Sciences (CAS) in Qingdao (1949-1958), Director of the Institute of Oceanology (CAS) in Qingdao (1959-1966), Director of the Institute of Zoology (CAS) in Beijing (1960-1962), member of CAS since 1955, Vice-Chairman of the Biological and Geographical Division of CAS (1955-1958), Chairman of the Biological Division of CAS (1959-1979) and Vice-President of CAS in Beijing (1978-1979). In spite of his administrative duties, he spent most of his life conducting bench work in his laboratories at the Institutes of Oceanology and Zoology, CAS, respectively, until he passed away in March 1979. Professor Tung's main research interest was with classic experimental studies on the determination of the egg axis and symmetry planes of fertilized eggs, early differentiation and organizing substances of egg cytoplasm, induction between embryonic cells and cytoplasm in embryogenesis, immunological studies on nuclear transplanted eggs, and cell fusion etc., in several types of animals. He conducted his experiments on a number of invertebrates (ascidians and Amphioxus) and vertebrates (fish and amphibians) by means of very skillful microsurgical operations and the nuclear transplantation method. Among these topics, his studies on the organization and developmental potency of Amphioxus eggs were unique. His important contribution to this research field involved not only establishing a practical method for collecting and using this rare animal for experimental purposes, but also clarifying controversy about the nature and early development of its eggs. He also provided conclusive evidence to determine its evolutionary position between invertebrates and vertebrates. The present article briefly reviews the main results obtained by Professor Tung and his colleagues on Amphioxus. Although their original articles were written both in Chinese and English, many international readers may not even know those original works because they were only published in scientific journals inside China from the 1950s. Comments and discussion on the experimental results of Amphioxus research by Tung's group and those from other earlier authors are also included.

Animals↗

Modified Campbell diagram to assess respiratory muscle action in speech.

Ten normal and four moderate to severe stutterers participated in the study. Pleural (Ppl) and abdominal (Pab) pressure was studied using oesophageal and gastric balloon catheter systems and VL (VL) was studied using magnetometry. The classical Campbell diagram was modified by plotting Pab versus VL. In a preliminary study we determined whether a surrogate curve could be substituted for the true curve in the Campbell diagram. We obtained true relaxation curves in six subjects. We obtained surrogate chest wall relaxation curves by joining the Pab value at functional residual capacity (FRC) to a point on the dynamic expiratory Pab, VL curve where Pab had decreased to half its maximum inspiratory excursion. In order to obtain the mirror image of the elastic recoil curve of the lung subjects breathed slowly from FRC to total lung capacity. Dynamic Pab, VL and Ppl, VL measurements during quiet breathing and speech were superimposed on static lung and chest wall curves. The simultaneous plot of Ppl and Pab provided a continuous measure of transdiaphragmatic pressure as a function of VL. We inferred non-diaphragmatic muscle recruitment vis-à-vis the diaphragm by the relationship of Pab to Ppl and Pab to the relaxation curve. We compared dynamic Ppl during phonation with that during breath-holding with the glottis open at the same VL, as an estimate of subglottic pressure (Psg). Analysis of variance testing showed that the true, surrogate and predicted relaxation slopes were not significantly different. The strategies that stutterers used to speak were either higher or lower VL than normal subjects and they had a different pattern of respiratory muscle recruitment. Stutterers were unable to achieve the appropriate degree of recruitment to develop and maintain a normal Psg for conversational speech and this contributed to dysfluency. We conclude that the quiet breathing loops can provide a reasonable approximation to the relaxation curve in normal healthy subjects and that modifications to the Campbell diagram provide useful means of measuring Psg and assessing respiratory muscle recruitment patterns.

Adolescent↗

Breathing responses to small inspiratory threshold loads in humans.

To investiage the effect of inspiratory threshold load (ITL) on breathing, all previous work studied loads that were much greater than would be encountered under pathophysiological conditions. We hypothesized that mild ITL from 2.5 to 20 cmH2O is sufficient to modify control and sensation of breathing. The study was performed in healthy subjects. The results demonstrated that with mild ITL 1) inspiratory difficulty sensation could be perceived at an ITL of 2.5 cmH2O; 2) tidal volume increased without change in breathing frequency, resulting in hyperpnea; and 3) although additional time was required for inspiratory pressure to attain the threshold before inspiratory flow was initiated, the total inspiratory muscle contraction time remained constant. This resulted in shortening of the available time for inspiratory flow, so that the tidal volume was maintained or increased by significant increase in mean inspiratory flow. On the basis of computer simulation, we conclude that the mild ITL is sufficient to increase breathing sensation and alter breathing control, presumably aiming at maintaining a certain level of ventilation but minimizing the energy consumption of the inspiratory muscles.

Adult↗

Perceived inspiratory difficulty during inspiratory threshold and hyperinflationary loadings.

Dynamic hyperinflation loads the inspiratory muscles by increasing end-expiratory lung volume (EELV) and imposing intrinsic positive end-expiratory pressure (PEEPi), the latter behaving as an inspiratory threshold load (ITL). The major purpose of this study was to describe the independent effects of the imposed ITL and changes in operating lung volume on the perception of inspiratory difficulty. In eight healthy subjects, independent increases in EELV and ITL were induced by continuous positive airway pressure (CPAP) and external ITL applications, respectively; increase in both EELV and PEEPi (thus the imposed ITL) was induced by application of positive end-expiratory pressure (PEEP). The perceived inspiratory difficulty increased significantly when either EELV or ITL was increased, and was always greater during combined increase in EELV and the imposed ITL (during PEEP) than when either factor was increased independently, suggesting that the imposed ITL and EELV each contribute independently to inspiratory difficulty. Inspiratory difficulty of each subject under all conditions was then fitted into a step-forward multiple regression model. The imposed ITL was a significant contributor to inspiratory difficulty in all subjects and was the first parameter to be selected in six of the eight subjects. When the results of all the subjects were pooled, the imposed ITL alone explained 40% of variations in inspiratory difficulty. Adding the change in end-inspiratory lung volume (DeltaEILV) to the model explained an additional 24% of variations in inspiratory difficulty. The coefficients (slopes) of the imposed ITL and DeltaEILV were 0.21 +/- 0.02 cm H2O-1 and 0.051 +/- 0.006 %IC-1, respectively. It is concluded that under our experimental conditions, the imposed ITL is a better predictor for explaining the variability of the perceived inspiratory difficulty than the operating lung volume.

Adult↗

Assessment of abdominal muscle contractility, strength, and fatigue.

We evaluated abdominal muscle contractility and fatigue by measuring twitch gastric pressure (Pgat) after percutaneous supramaximal electrical stimulation of the abdominal wall before and after sit-ups to task failure. Mouth pressures during maximal voluntary expulsive maneuvers (PEmax) at TLC and FRC with superimposed twitches, and maximum voluntary ventilation (MVV) were also assessed. Mean fresh Pgat was 36.1 +/- 3.0 cm H2O with a coefficient of variation that ranged between 3.0 to 4.8%. Pgat decreased by 25% (p < 0.001) and 37% (p < 0.001) at 1 and 30 min after sit-ups. During maximal voluntary contraction twitch occlusion never occurred. PEmax at TLC and FRC decreased by 15% (p < 0.001) and 11% (p < 0.017) at 1 min, and 8% (p < 0.036) and 9% (p < 0.030) at 30 min after sit-ups, respectively. Despite the abdominal muscle fatigue, MVV values at 1 and 30 min after sit-ups were not significantly different from the value obtained before the sit-ups. We conclude that (1) Pgat is a useful objective indicator of abdominal muscle contractility and fatigue; (2) during maximal voluntary expulsive maneuvers the abdominal muscles are never fully activated; (3) sit-ups lead to substantial low-frequency fatigue but little high-frequency fatigue of the abdominal muscles, which has little effect on maximal breathing capacity.

Abdominal Muscles↗

Sensation of inspiratory difficulty during inspiratory threshold and hyperinflationary loadings. Effect of inspiratory muscle strength.

Dynamic hyperinflation loads the inspiratory muscles by increasing end-expiratory lung volume (EELV) and imposing intrinsic positive end-expiratory pressure (PEEPi), the latter behaving as an inspiratory threshold load (ITL). The aim of the current study was to examine how induced-inspiratory muscle fatigue affects the independent effects of the imposed ITL and increasing operating lung volume on the perceived inspiratory difficulty. Dynamic hyperinflation in healthy subjects was induced by positive end-expiratory pressure (PEEP). Increasing operating lung volume alone (without PEEPi) and increasing ITL alone (without change in EELV) were induced by continuous positive airway pressure (CPAP) and external ITL, respectively. Inspiratory difficulty was quantified by the modified Borg scale and analyzed by step forward multiple regression, using the imposed ITL, EELV, and end-inspiratory lung volume (EILV) as independent variables. When fresh, the first entered variable was the imposed ITL (r(2), 0.38). Adding EILV into the model increased r(2) to 0.67. After fatigue, the first entered variable became EILV (r(2), 0.50) and the second selected variable was the imposed ITL, which increased r(2) to 0.66. EELV was insignificant under both conditions. The coefficient of EILV increased significantly from 0.039 +/- 0.005 to 0.092 +/- 0.012 (% inspiratory capacity(-)(1)) after fatigue run (p < 0.001), whereas that of the imposed ITL did not change. It is concluded that in the experimental conditions studied, inspiratory muscle fatigue increased the importance of lung volume over that of inspiratory threshold load in determining the perceived inspiratory difficulty.

Humans↗

Perturbation of EGF-induced MAP kinase activation by TGF-beta 1.

TGF-beta 1 regulates both cellular growth and phenotypic plasticity important for maintaining a growth advantage and increased invasiveness in progressively malignant cells. Recent studies indicate that TGF-beta-1 stimulates the conversion of epitheliod to fibroblastoid phenotype which presumably leads to the inactivation of growth-inhibitory effects by TGF-beta 1 (Portella et al. (1998) Cell Growth and Differentiation, 9: 393-404). Therefore, the investigation of TGF-beta 1 signaling that leads to altered growth and migration may provide novel targets for the prevention of increased cell growth and invasion. Although much attention has been paid to TGF-beta 1 responses in epithelial cells, the above studies suggest that examination of signal transduction pathways in fibroblasts are important as well. Data from our laboratory are consistent with the concept that TGF-beta 1 can act as a regulatory switch in density-dependent C3H 10T1/2 fibroblasts capable of either promoting or delaying G1 traverse. The regulation of this switch is proposed to occur prior to pRb phosphorylation, namely prior to activation of cyclin-dependent kinases. The current study is concerned with the evaluation of a key cyclin (cyclin D1) which activates cdk4 and p27KIP1 which in turn inhibit cdk2 in the proliferative responses of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) and their modulation by TGF-beta 1. Although the molecular events that lead to elevation of cyclin D1 are not completely understood, it appears likely that activation of p42/p44MAPK kinases is involved in its transcriptional regulation. TGF-beta 1 delayed EGF- or PDGF-induced cyclin D1 expression and blocked the induction of active p42/p44MAPK. The mechanism by which TGF-beta 1 induces a block in p42/p44MAPK activation is being examined and the possibility that TGF-beta 1 regulates phosphatase activity is being tested.

Cell Transformation, Neoplastic↗

Association of polymorphism of apolipoprotein E gene with coronary heart disease in Han Chinese.

OBJECTIVE: To investigate the association between apolipoprotein E (apoE) gene polymorphism and coronary heart disease(CHD) in Han Chinese. METHODS: Apo E genotype was examined with the methods of hot start polymerase chain reaction (PCR) and restriction isotyping in samples of 113 unrelated Chinese healthy individuals and 93 patients with CHD. The relation of the gene polymorphism of apoE and levels of serum lipids, lipoproteins, and apolipoproteins was also studied. RESULTS: The results showed that the epsilon 4/3 genotype was more frequent in CHD cases than in control subjects (31.2% vs. 11.5%, P < 0.01). The frequency of the epsilon 4 allele in CHD cases was significantly higher than in control subjects (17.2% vs 7.5%, P < 0.01). The epsilon 4 allele was associated with high concentrations of serum TC (r = 0.265, P < 0.05), LDL-C (r = 0.266, P < 0.05), and apoB (r = 0.360, P < 0.01). CONCLUSIONS: Hot start PCR assay is considered a rapid and simple technique for apoE genotyping. This method is suitable for routine laboratories and large scale population studies. Genetic polymorphism of the apoE gene might contribute to the determination of serum lipid profile and the development of CHD among Han Chinese.

Alleles↗

Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans. Identification of a common receptor for fibronectin, fibrinogen, and laminin.

Host infection by the pathogenic fungus Candida albicans is initiated by adhesion and mediated by binding to several host extracellular matrix proteins. Previously, we demonstrated that hemoglobin supplemented into a chemically defined medium significantly and specifically induced fibronectin binding to C. albicans. We now report that hemoglobin also induces binding of laminin, fibrinogen, and type IV collagen but not of thrombospondin-1 or type I collagen. The binding of each protein was inhibited by the respective unlabeled ligand in a concentration-dependent manner. Fibrinogen inhibited the binding of radiolabeled fibronectin, laminin, and fibrinogen with similar IC50 values, suggesting that a single promiscuous receptor recognizes these three proteins. Competitive binding studies indicated that a second class of receptor binds specifically to laminin. Growth of C. albicans in the presence of hemoglobin also increased cell adhesion to immobilized fibronectin, laminin, fibrinogen, and type IV collagen but not to thrombospondin-1 or type I collagen. Exposure to hemoglobin induced increased or de novo expression of several surface proteins on C. albicans. One of these proteins with a molecular weight of 55,000 recognized fibronectin, based on ligand protection and affinity chromatography on immobilized fibronectin. Thus, hemoglobin induces both promiscuous and specific receptors for extracellular matrix proteins and, therefore, may regulate matrix adhesion during dissemination of C. albicans infections.

Binding, Competitive↗

Voltage- and use-dependent effect of 7-chlor-benzyltetrahydropalmatine on sodium currents in guinea pig ventricular myocytes.

The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzyltetrahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7.8 +/- 1.8 nA to 5.3 +/- 1.4 nA, P < 0.01, n = 5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V0.5 was shifted from -(82.5 +/- 2.5) mV to -(95 +/- 2.4) mV (P < 0.05, n = 4). 7-Cl-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-Cl-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-Cl-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.

Animals↗