Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

Female gender is associated with an increasedrisk of drug-associated torsade de pointes (TdP) .Many kinds of drugs such as class ⅠAand class Ⅲantiarrhythmia , some antibiotics , antidepressantdrugs have the potential of inducing TdP. It isthought that the slower repolarization of femaleheart accounts for the higher incidence of TdP.However ,the current difference between male andfemale is poorly known. Our previous experi menthas shown that rabbits presented the same differ-ence of TdP a…     

Electrophysiological study of V535M hERG mutation of LQT2

This study examined the current changes of human ether-a-go-go-related gene (hERG) mutation derived from a LQT2 Chinese family with a highly penetrating phenotype.Mutation was identified and site-direc...     

Effect of Nitric Oxide on Potassium Channels of Rat Airway Smooth Muscle Cells

Summary: The effect of nitric oxide donor sodium nitroprusside (SNP) on resting membrane potential (Em) and potassium currents of the bronchial smooth muscle cells from rats was investigated. All experiments were conducted in conventional whole-cell configuration. The changes of Em and potassium currents after addition of 0. 1 mmol/L SNP were measured under the current-clamp mode and the voltage-clamp mode respectively. Results showed that (1) SNP could decrease the Em from --33. 8±7.4 mV to -43. 7±6. 7mV (n=10, P＜0. 01); (2) SNP could increase the Ca2+-activated K+ channel peak currents under ramp protocol from 466.9±180. 1 pA to 597. 7±237. 6 pA (n= 7, P＜0. 01), and the currents under pulse protocol at +50 mV were increased from 544.2±145.4 pA to 678.1±206. 2 pA (n=6, P＜0.05); (3) SNP also could increase voltage-gated K+ channel peak currents under ramp protocol from 389. 6±84. 1 pA to 526. 7±98. 7 pA (n=7, P＜0. 01), the currents under pulse protocol at +50 mV were increased from 275.7±85.2 pA to 444.3±128.5 pA(n=6,P＜0. 01). It was concluded that SNP increases the activities of Ca2+-activated K+ channels and voltage-gated K+ channels and leads to K+ efflux and hyperpolarization of the cell membrane, resulting in a decrease of the cell excitement.     

犬左右心室肌细胞L型钙电流不均一性的研究

目的测定犬左、右心室3层心肌细胞上参与离子流平衡的内向电流L型钙电流(ICa.L)的特性。方法经酶解分离获得犬左、右心室外膜下细胞、M细胞和内膜下细胞,应用全细胞膜片钳技术,记录并比较不同部位心肌细胞的ICa.L,分析电流-电压曲线。结果ICa.L的峰值电流密度(pA/pF)在右心室外膜下细胞、M细胞和内膜下细胞分别为:-4.896±1.907(n=31),-3.406±0.904(n=37)和-2.788±0.756(n=33),心外膜下心肌细胞与M细胞比较,差异有统计学意义(P<0.05);在左心室分别为:-3.824±1.201(n=18),-4.854±1.485(n=20)和-2.988±1.082(n=17),3者之间两两比较,差异有统计学意义(P<0.05)。ICa.L的峰值电流密度在右心室心外膜下心肌细胞大于左心室(P<0.05),而右心室M细胞小于左心室(P<0.01),心内膜下心肌细胞左、右心室之间差异无统计学意义(P>0.05)。结论ICa.L在犬左、右心室肌的不同细胞(外膜下心肌细胞、M细胞、内膜下心肌细胞)存在不均一性,导致右心室跨室壁的电不均一性较左心室明显。     

Effects of Phorbol-12,13-dibuterate on Sodium Currents and Potassium Currents in Rat Trigeminal Ganglion Neurons

The effects of phorbol-12,13-dibuterate (PDBu) on total sodium current (INa-total), tet-rodotoxin-resistant sodium current (INa-TTXr), 4-AP-sensitive potassium current (IA) and TEA-sensitive potassium current (IK) in trigeminal ganglion (TG) neurons were investigated. Whole-cell patch clamp techniques were used to record ion currents in cultured TG neurons of rats. Results revealed that 0.5 μmol/L PDBu reduced the amplitude of INa-total by (38.3±4.5)% (n=6, P<0.05), but neither the G-V curve (control: V0.5 =-17.1±4.3 mV, k=7.4±1.3; PDBu: V0.5=-15.9±5.9 mV, k=5.9±1.4; n=6, P>0.05) nor the inactivation rate constant (control: 3.6±0.9 ms; PDBu: 3.6±0.8 ms; n=6, P>0.05) was altered. 0.5 μmol/L PDBu could significantly increase the amplitude of INa-TTXr by (37.2± 3.2)% (n=9, P<0.05) without affecting the G-V curve (control: V0.5=-14.7±6.0 mV, k=6.9± 1.4; PDBu: V0.5=-11.1±5.3 mV, k=8.1±1.5; n=5, P>0.05) or the inactivation rate constant (control: 4.6±0.6 ms; PDBu: 4.2±0.5 ms; n=5, P>0.05). 0.5 μmol/L PDBu inhibited IK by (15.6±5.0) % (n=16, P<0.05), and V0.5 was significantly altered from - 4.7±1.4 mV to -7.9 ±1.8 mV (n=16, P<0.05). IA was not significantly affected by PDBu, 0.5 μmol/L PDBu decreased IA by only (0.3±3.2)% (n=5, P>0.05). It was concluded that PDBu inhibited INa-total but enhanced INa-TTXr, and inhibited IK without affecting IA. These data suggested that the activation of PKC pathway could exert the actions.     

Bioequiwalence of clavulanate Potassium and Amoxicillin（1：7）dispersible tablets in healthy volunteers

Summary To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1∶7) dispersible tablets, a randomized cross—over study was conducted in 18 healthy volunteers. A single oral dose of 1000 mg Clavulanate Potassium and Amoxicillin (1∶7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main paramaters of T were: for Clavulanate Potassium and Amoxicillin, C_max: 2.46±1.11 μg/ml and 18.81±7.26 μg/ml, T_max: 1.12±0.23h and 1.30±0.34h, ACU_(0–6h): 5.18±2.24 μg·h/ml and 45.09±14.53 μg·h/ml, t_1/2: 1.43±0.44 h and 1.09±0.22 h., respectively. The relative bioavailability of T to R were 96.5±19.2% and 98.4±26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent. HU Guoxin, male, born in 1957, Associate Professor     

Electrical remodeling of membrane ionic channels of hypertrophied ventricular myocytes from spontaneously hypertensive rats

Ｍｅｔｈｏｄｓ　Ｍｅｍｂｒａｎｅｉｏｎｉｃｃｈａｎｎｅｌｓｗｅｒｅｓｔｕｄｉｅｄｉｎｅｎｚｙｍａｔｉｃａｌｌｙｄｉｓｐｅｒｓｅｄｓｐｏｎｔａｎｅｏｕｓｌｙｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓ (ＳＨＲｓ)ｌｅｆｔｖｅｎｔｒｉｃｕｌａｒｍｙｏｃｙｔｅｓｕｓｉｎｇｔｈｅｗｈｏｌｅ ｃｅｌｌｃｏｎｆｉｇｕｒａｔｉｏｎｏｆｐａｔｃｈ ｃｌａｍｐｔｅｃｈｎｉｑｕｅ ,ｗｉｔｈｎｏｒｍａｌＷｉｓｔａｒｒａｔｓｖｅｎｔｒｉｃｕｌａｒｍｙｏｃｙｔｅｓａｓｃｏｎｔｒｏｌｓ Ｗｅｏｂｓｅｒｖｅｄｄｅｐｏｌａｒｉｚｉｎｇｃｕｒｒ…     

Effect of Shengmai injection (生脉注射液) on vascular endothelial and heart functions in patients with coronary heart disease complicated with diabetes mellitus

Objective： To study the effect of Shengmai injection （生脉注射液, SMI） on vascular endothelial and heart functions in coronary heart disease patients complicated with diabetes mellitus （CHD-DM）. Methods： One hundred and twenty patients with CHD-DM, their diagnosis confirmed by coronary arteriography, were equally randomized into a control group treated with conventional treatment and a treated group treated with conventional treatment plus SMI. The changes in blood levels of nitric oxide （NO）, endothelin-1 （ET-1） and angiotensin Ⅱ （Ang Ⅱ）, as well as endothelium-dependent vascular dilating function and heart function in the patients were observed before treatment and after the 3-week treatment. Results： After being treated with SMI for 3 weeks, in the treated group, blood level of NO was raised significantly from 69.8±33.1 μmol/L to 120.1±50.8μmol/L, and ET-1 was lowered from 70.1±32.1 ng/L to 46.2±21.3 ng/L, respectively （P〈0.01）; that of Ang Ⅱ was lowered from 81.3±24.3 ng/L to 50.2±27.3 ng/L （P〈0.01）; brachial arterial post-congestion blood flow increasing rate was raised from 389.4±26.3% to 459.3±27.8% （P〈0.01）; and the improvement in heart function as seen through the ejection fraction （EF） was increased from 44±5% to 68±6% （P〈0.01）, all the changes being more significant than those in the control group （all P〈0.01）. Conclusion： SMI can improve not only the endothelial function in CHD-DM patients, but also heart contraction significantly.     

淫羊藿苷对兔心室肌细胞L-型钙电流的影响

目的:利用膜片钳技术研究淫羊藿苷(ICA)对兔单个心室肌细胞L-型钙电流(ICa,L)的影响。方法:采用酶解法分离兔单个心室肌细胞,应用全细胞膜片钳技术观察10,20,40μmol/L的ICA对心室肌细胞ICa,L的作用。结果:①10,20,40μmol/L的ICA使兔心室肌细胞ICa,L最大峰电流密度从(15.81±1.23)pA/pF分别降至(11.27±0.89)pA/pF,(9.48±0.85)pA/pF和(6.87±0.81)pA/pF(n=6,P<0.05),抑制率分别为28.7%,40.0%和56.5%;ICA使ICa,L的电流-电压曲线上移,但不改变其基本形状;②20μmol/L ICA可以使钙通道稳态失活曲线左移并可减慢L-型钙通道失活后的恢复过程。结论:ICA对ICa,L具有浓度依赖性阻滞作用,这可能是其抗心律失常的重要机制之一。     

Placental Isoferritin Action in Pathogenesis of Pre-eclampsia and/or Intrauterine Growth Retardation and Its Earlier Predictive Value

Pre- eclampsia and intrauterine growth retarda-tion(IUGR) are major sources of clinical morbidityand mortality in pregnant women and prenatal in-fants.Their mechanisms are not completely clear.The imbalance of maternal- fetal immune interactionwas demonstrated to play a role in them[1] .Recentlyplacental isoferritin (PLF) was demonstrated to be asignificant immune regular factor in pregnant im-mune inhibition[2 ] ,butitsrole in pathogenesisof pre-eclampsia and/or IUGR is unknown.In this s…     

Long-term effects of imidapril on calcium and potassium currents in rabbit left ventricular hypertrophic myocytes

Cardiachypertrophy ,inducedby pressureoverload ,isassociatedwithalterationsintheelectrophysiologicpropertiesoftheheart,whichmaycontributetotheincreasedincidenceofventriculararrhythmias 1,2 Amongmanyfactorsinducinghearthypertrophy ,therenin angiotensinsystem (RAS) playsanimportantroleintheregulationofcardiaccellsandmatrixgrowth AngiotensinⅡlevelcanbepartiallyreducedafteradministrationofangiotensinconvertingenzyme (ACE)inhibitors ACEinhibitorshavebeenshowntodecreaseventricularhypertrophyandr…     

The role of neutrophil activation in pathogenesis of preeclampsia

Pre- eclampsia,a common pregnancy complica-tion,isone of the leading causesof maternal mortali-ty and perinatal mortality and modality.The patho-genesis of this disease remains unclear.Endothelialdamage,which appears to be common to the patho-physiologicalfeatures of pre- eclampsia,has been doc-umented[1] .However,neutrophil activation may playan importantrole in vascular endothelium damage[2 ] .In this study,the CD1 1 b expression was examinedby using flow cytometry,and the levelsof plasma e…     

Antagonistic effects of trasilast on proliferation and collagen synthesis induced by TGF-\sB<Subscript>2</Subscript> in cultured human trabecular meshwork cellsin cultured human trabecular meshwork cells

Summary Whether tranilast had antagonistic effect on proliferation inhibition and collagen synthesis promotion induced by TGF-\sB₂ in cultured human trabecular meshwork cells was investigated. Suspension of 1×10⁴ cultured human trabecular meshwork cells of 3–5 passage was distributed in each well of a 96-well disk and divided into control group and experimental group. After 24 h, 0 μg/ml (control), 12.5 μg/ml, 25 μg/ml, 50μg/ml tranilast with 3.2 ng/ml TGF-\sB₂ were added into the incubation medium. Another 24 h later, proliferation and collagen synthesis in cultured human trabecular meshwork cells were examined respectively by using tetrazolium-based semiautomated colormetric (MTT) assay and³H-proline incorporation with liquid scintillation technique. The results showed absorbance (A) values of the experimental groups were 0.9036±0.3017, 1.1361±0.1352, 1.2457±0.1524 according to the different concentrations of tranilast, and 0.8956±0.1903 of the control group. In comparison with the control group, 25 μg/ml (q=3.23,P<0.05), 50 μg/ml (q′=4.70,P<0.01) tranilast significantly antagonized the decrease of theA values induced by TGF-\sB₂ in the cultured human trabecular meshowrk cells. In comparison with the control group [817.37±124.21 cpm/10⁴ cells], 12.5 μg/ml (620.33±80.46 cpm/10⁴ cells,q′=4.26,P<0.05), 25 μg/ml (59.4.58±88.13 cpm/10⁴ cells,q′=4.81,P<0.01), 50 μg/ml (418.64±67.90 cpm/10⁴ cells,q′=8.62,P<0.01) tranilast significantly inhibited the incorporation of³H-proline into the cultured human trabecular meshwork cells promoted by TGF-\sB₂ in a dose-dependent manner. It was concluded that tranilast had the antagonistic effect on the proliferation inhibition and collagen synthesis promotion induced by TGF-\sB₂ in the cultured human trabecular meshwork cells. Da Banghong, female, born in 1973, Resident. This project was supported by a grant from the National Natural Sciences Foundation of China (No. 38970758).     

The Changes of Potassium Currents in Rabbit Ventricle with Healed Myocardial Infarction

Epidemiologicalstudiesshowedthatpatientswithhealmyocardialinfarction (HMI)arethemainpopula tionofcardiacsuddendeath .CASTtrial[1 ] andSWORDtrial[2 ] hadaprofoundimpactonthepracticeofcardiolo gy,andthemortalitywassignificantlyhigherinpatientswithHMItreated…     

Measurement of platelet-activating factor in human blood by high performance thin layer chromatography and its clinical application

Summary Platelet-activating factor (PAF) present in the blood of the patients with chronic pulmonary heart disease and asthma has been detected by high performance thin layer chromatography (HPTLC). The patients with chronic pulmonary heart disease accompanied by carbon dioxide retention (PaCO₂>6.67 kPa) have a higher level of PAF in blood (0. 75 ±0. 27 μg/ml) than those who have no carbon dioxide retention (PaCO₂<6.67 kPa, PAF 0.41 ±0. 25 μg/ml) and those in the normal control group (0.45 ±0.20 μg/ml), withP<0.05 in all. The patients with asthma have a higher PAF in blood (0.83±0. 05 μg/ml) than those in the control group (P < 0.005). These findings suggest that PAF plays an important role in episodes of chronic pulmonary heart disease and asthma.     

Endothelial nitric oxide synthase traffic inducer in the umbilical vessels of the patients with pre-eclampsia

The expression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） was examined in the umbilical vessels of the patients with pre-eclampsia （PE） to explore its possible role in the pathogenesis of PE. The NOSTR1N rnRNA in umbilical tissues was determined by RT-PCR. The eNOS activity in umbilical vessels was spectrophotometrically detected. NO2 /NO3, the stable metabolic end products of NO, was measured by using nitrate reductase. RT-PCR showed that the expression level of NOSTRIN was significantly higher in women with PE than in the normal group （P〈0.01）. The activity of eNOS was significantly decreased in PE group [（12.83±3.61） U/mg] than in normal group [（21.72±3.83） U/mg] （P〈0.01）. The level of NO2-/NO3- in PE patients （27.53±7.48） pmol/mg was significantly lower than that of normal group （54.27±9.53） μmol/mg （P〈0.01）. The significant negative correlation existed between the expression of NOSTRIN and the activity of eNOS in umbilical vessels of women with PE （r=-0.58, P〈0.01）. It was concluded that the level of NOSTR1N expression was increased in umbilical vessel of women with PE, indicating that it may be involved in the pathogenesis of PE.     

Expression of Endothelial Nitric Oxide Synthase Traffic Inducer in the Placenta of Pregnancy Induced Hypertension

Endothelial nitric oxide synthase traffic induc-er(NOSTRIN),a58kD(1kD=0.9921ku)pro-tein with complete unknown function that was i-dentified using the yeast two-hybrid system byZi mmermannet al[1],and Zi mmermann demon-strated that NOSTRIN over-expression induced aprofound redistribution of eNOS fromthe plasmamembrane to vesicle-like structures matching theNOSTRIN pattern and at the same ti me led to asignificant inhibition of NO release[1].WhetherNOSTRIN do involve in the mechani…     

Effects of WIN 55,212-2 on IK Current in Cultured Trigeminal Ganglion Neurons of Rat

Summary To investigate the effects of WIN 55, 212-2 onI _K in cultured rat trigeminal ganglion (TG) neurons, whole-cell patch clamp techniques were used to record theI _K before and after WIN 55,212-2 perfusion at different concentrations. 30 μmol/L WIN 55,212-2 markedly (35.7%±7.3%P<0.01,n=8) inhibitedI _K currents, and the currents were partially recovered after washing. 30 μmol/L WIN 55, 212-2 also induced a significant depolarizing shift in conductance-voltage parameters (control: V_0.5=10.43±4.25 mV, k=16.27±3.86; WIN 55,212-2: V_0.5=24.71±3.91 mV, k=16.69±2.75;n=8,P<0.01 for V_0.5). 0.01 μmol/L WIN 55,212-2 slightly (27.0%±7.9%,P<0.05,n=7) increasedI _K currents, but had no significant change in conductance-voltage parameters (control: V_0.5=10.74±5.27 mV, k=17. 33±2.96; WIN 55, 212-2: V_0.5=11.06±2.05 mV, k=19.69±6.60;n=7,P>0.05 for V_0.5 and k). These results suggested that WIN 55, 212-2 has dual action, which might be through different receptors. MING Zhangyin, male, born in 1968, Doctorial Candidate This project was supported by a grant from National Natural Sciences Foundation of China (No. 30271500).     

M_3R介导的cAMP-PKA信号途径对L-型钙通道的调控作用研究

目的研究M3受体激动剂通过cAMP-PKA信号途径对L-型钙通道的影响。方法应用全细胞膜片钳技术记录M3受体激动剂胆碱对大鼠单个心室肌细胞L-型钙通道电流(ICa-L)的影响;采用激光扫描共聚焦技术观察细胞内钙离子的变化。结果胆碱使大鼠心室肌细胞ICa-L密度从(9.07±0.68)pA/pF减少至(5.58±0.62)pA/pF(n=4,与对照组相比,P<0.01),H89加胆碱组使ICa-L电流密度减少至(7.68±0.75),幅度明显高于胆碱组(n=4,与胆碱组相比,P<0.01)。胆碱抑制KCl除极诱导的心肌细胞[Ca2+]i的升高,从(2.83±0.08)降至(1.17±0.09)FI/FI0(n=30,与KCl组相比,P<0.01),胆碱与H89组可使[Ca2+]i降至(1.65±0.17)FI/FI0,幅度高于胆碱组(n=30,与胆碱组相比,P<0.05)。结论 M3受体激动剂胆碱通过抑制PKA活性调控L-型钙通道,使外钙内流减少,降低细胞[Ca2+]i,从而发挥抗心肌保护作用。     

心房峡部L型钙电流特征的研究

目的研究心房峡部L型钙电流的特性,探讨心房峡部参与心律失常的机制。方法新西兰大白兔15只,麻醉后取心脏,灌流后分离右心房峡部及游离壁,利用全细胞膜片钳技术,对比观察心房峡部和右心房游离壁L型钙电流的电流密度,并观察异丙肾上腺素灌流后,其电流密度的变化。结果正常状态下,心房峡部和右心房游离壁L型钙电流的电流密度分别为-(7.03±0.71)pA/pF、-(6.30±0.61)pA/pF,二者比较差异无显著意义(P>0.05)。异丙肾上腺素灌流后,心房峡部和右心房游离壁L型钙电流的电流密度分别为-(11.01±0.46)pA/pF、-(8.51±0.31)pA/pF,两处的L型钙电流均显著增大,且心房峡部的L型钙电流密度显著大于右心房游离壁(P<0.01)。结论L型钙电流的异常变化可能是心房峡部参与心律失常发生机制的重要因素。