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1.
Using the standard voltage-clamp technique in the whole-cell mode, we studied the characteristics of barium currents (I Ba; Ba2+ concentration in the external solution was 5 mM) carried through L-type Ca2+ channels in the membrane of myocytes of the resistive mesenteric artery from normotensive and genetically hypertensive rats (NR and GHR, respectively). To perforate the membrane, we used amphotericin B. The arbitrary density of I Ba through the plasma membrane of GHR myocytes significantly exceeded this parameter in the NR group. For both animal groups, activation curves plotted as the dependence of the membrane conductance (G Ba) on the membrane potential were not significantly different: the membrane potential for half activation (V 0.5) of I Ba in the NR myocytes was equal to 1.0 ± 0.3 mV with slope factor k = 6.3 ± 0.4 mV, whereas in the GHR myocytes V 0.5 = -1.6 ± 0.2 mV and k = 6.2 ± 0.5 mV. The stationary inactivation curves for I Ba differed significantly: in the NR myocytes, V 0.5 = -24.2 ± 0.4 mV and k = 8.3 ± 0.2 mV, whereas in the GHR myocytes such parameters were, respectively, -21.4 ± 0.4 and 8.7 ± 0.3 mV. The pattern of intersection of stationary activation and stationary inactivation curves for I Ba was indicative of the existence of a window current, i.e., the non-inactivating component of I Ba within the -40 to ±20 mV range; the phenomenon was clearly pronounced in the GHR myocytes. Differences in the arbitrary density of integral I Ba and window current were observed. These differences can cause an increased tone of the blood vessels in hypertensive animals.  相似文献   

2.
Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. Therefore, we investigated the effect of bindarit on human coronary smooth muscle cells activation, drawing attention to the phenotypic modulation process, focusing on contractile proteins expression as well as proliferation and migration. The expression of contractile proteins was evaluated by western blot analysis on cultured human coronary smooth muscle cells stimulated with TNF-α (30 ng/mL) or fetal bovine serum (5%). Bindarit (100–300 µM) reduced the embryonic form of smooth muscle myosin heavy chain while increased smooth muscle α-actin and calponin in both TNF-α- and fetal bovine serum-stimulated cells. These effects were associated with the inhibition of human coronary smooth muscle cell proliferation/migration and both MCP-1 and MCP-3 production. The effect of bindarit on smooth muscle cells phenotypic switching was confirmed in vivo in the rat balloon angioplasty model. Bindarit (200 mg/Kg/day) significantly reduced the expression of the embryonic form of smooth muscle myosin heavy chain, and increased smooth muscle α-actin and calponin in the rat carodid arteries subjected to endothelial denudation. Our results demonstrate that bindarit induces the differentiated state of human coronary smooth muscle cells, suggesting a novel underlying mechanisms by which this drug inhibits neointimal formation.  相似文献   

3.
A 17-year-old boy had a 2-day prodrome of fever and mild sore throat followed by 2 episodes of severe anginal chest discomfort and substantial transient ST-segment elevations in the anterior leads of the electrocardiogram. A subsequent evaluation showed the 2 episodes were most likely coronary vasospasm complicating acute viral myocarditis.  相似文献   

4.
Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare, and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K+) channels to infect cells. Time of addition assays using K+ channel modulating agents demonstrated that K+ channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K+ channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, two-pore domain K+ channels (K2P) were identified as the K+ channel family mediating BUNV K+ channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease.  相似文献   

5.
Stress in the lipids of the cell membrane may be responsible for activating stretch-activated channels (SACs) in nonspecialized sensory cells such as cardiac myocytes, where they are likely to play a role in cardiac mechanoelectric feedback. We examined the influence of the mechanical microenvironment on the gating of stretch-activated potassium channels (SAKCs) in rat atrial myocytes. The goal was to examine the role of the cytoskeleton in the gating process. We recorded from blebs that have minimal cytoskeleton and cells treated with cytochalasin B (cyto-B) to disrupt filamentous actin. Histochemical and electron microscopic techniques confirmed that the bleb membrane was largely free of F-actin. Channel currents showed mechanosensitivity and potassium selectivity and were activated by low pH and arachidonic acid, similar to properties of TREK-1. Some patches showed a time-dependent decrease in current that may be adaptation or inactivation, and since this decrease appeared in control cells and blebs, it is probably not the result of adaptation in the cytoskeleton. Cyto-B treatment and blebbing caused an increase in background channel activity, suggesting a transfer of stress from actin to bilayer and then to the channel. The slope sensitivity of gating before and after cyto-B treatment was similar to that of blebs, implying the characteristic change of dimensions associated with channel gating was the same in the three mechanical environments. The mechanosensitivity of SAKCs appears to be the result of interaction with membrane lipids and not of direct involvement of the cytoskeleton.  相似文献   

6.
目的观察开胸结扎冠状动脉与闭胸明胶海绵栓塞法制备急性心肌梗死(AMI)动物模型的特点。方法分别经开胸结扎犬冠状动脉左前降支主干及闭胸冠脉栓塞的方法阻断冠脉血流;采用单级肢体导联和胸导联方式,在阻断前后监测心电图波形变化;造模72h后取心肌组织行病理切片染色。结果经心电图和病理验证,两种方法均可成功制备犬心梗模型,开胸冠脉结扎犬死亡率较高,而冠脉栓塞成活率高。结论相较开胸冠脉结扎法,闭胸栓塞法制备心梗模型对动物损伤小,成活率高,具推广价值。  相似文献   

7.
The effects of thyroid status on the properties of ATP-sensitive potassium channels were investigated. Single-channel recordings were made using excised inside-out membrane patches from enzymatically dissociated ventricular myocytes from hearts of control and thyroidectomized rats and each group was studied with and without administration of thyroid hormone. In patches excised from hypothyroid myocytes the IC50 for ATP inhibition of KATP channels was 110 μm. This value was 3-fold higher than the IC50 in control myocytes (43 μm). Treatment of hypothyroid rats to restore physiological levels of thyroid hormone (tri-iodothyronine, T3), resulted in a return to normal ATP-sensitivity (IC50= 46 μm). In patches from animals rendered hyperthyroid, the IC50 for ATP was 50 μm and this value was not significantly different from the control. There was no difference in the cooperativity of ATP-binding (Hill coefficient, nH) among control (nH= 2.2), hypothyroid (nH= 2.1), T3-treated (nH= 2.0) and hyperthyroid groups (nH= 2.4). The unitary conductance was unchanged and there was no apparent change in intraburst kinetics between examples of single KATP channels from control and hypothyroid rats. Action potentials recorded in myocytes from hypothyroid rats were significantly shortened by 50 μm levcromakalim, a KATP channel opener (P < 0.001) but unchanged in control myocytes. We conclude that hypothyroidism significantly decreased the ATP-sensitivity of KATP channels, whereas the induction of hyperthyroid conditions did not alter the ATP-sensitivity of these channels. Thus, hypothyroidism is likely to have important physiological consequences under circumstances in which KATP channels are activated, such as during ischemia. Received: 1 July 1997/Revised: 24 December 1997  相似文献   

8.
目的应用心导管介入方法封堵冠状动脉制备兔急性心肌梗死模型。方法选择雄性新西兰兔,先行冠状动脉造影,利用导引钢丝将微导管置于左前降支远端,将高分子栓塞剂与碘油混合配制成封闭胶,经微导管注入血管,造成急性心肌梗死。术前、术中和术后l周记录心电图变化。实验终点切取心肌组织标本分别行苏木素一伊红(H.E)染色、氯化硝基四氮唑蓝(NBT)染色、免疫组化染色。结果造模动物20只,存活16只。冠脉造影显示封闭胶持续滞留于左前降支远端,提示血管完全堵塞。心电图提示存在动态变化,ST段抬高,病理性Q波逐渐形成。心脏大体观测提示左心室前侧壁呈灰白色为梗死区。E染色提示梗死区局部纤维组织增生、疤痕形成、钙盐沉积,缺血区肌束变性、炎症细胞浸润,符合典型心肌梗死的病理变化。NBT染色后测定梗死面积为28.32%±5.21%。免疫组化染色提示缺血区CD34阳性面积和血管新生密度明显高于梗死区及正常组织区(P〈0.05)。结论通过心导管介入方法制备兔急性心肌梗死模型成功,避免了开胸损伤对实验结果的影响,更符合临床急性心肌梗死的病理特点。  相似文献   

9.
The effects of verapamil on the large conductance Ca-activated K (BK) channel from rat aortic smooth muscle cells were examined at the single channel level. Micromolar concentrations of verapamil produced a reversible flickering block of the BK channel activity. Kinetic analysis showed that verapamil decreased markedly the time constants of the open states, without any significant change in the time constants of the closed states. The appearance of an additional closed state — specifically, a nonconducting, open-blocked state — was also observed, whose time constant would reflect the mean residence time of verapamil on the channel. These observations are indicative of a state-dependent, open-channel block mechanism. Dedicated kinetic (group) analysis confirmed the state-dependent block exerted by verapamil. D600 (gallopamil), the methoxy derivative of verapamil, was also tested and found to exert a similar type of block, but with a higher affinity than verapamil. The permanently charged and membrane impermeant verapamil analogue D890 was used to address other important features of verapamil block, such as the sidedness of action and the location of the binding site on the channel protein. D890 induced a flickering block of BK channels similar to that observed with verapamil only when applied to the internal side of the membrane, indicating that D890 binds to a site accessible from the cytoplasmic side. Finally, the voltage dependence of D890 block was assessed. The experimental data fitted with a Langmuir equation incorporating the Woodhull model for charged blockers confirms that the D890-binding site is accessed from the internal mouth of the BK channel, and locates it approximately 40% of the membrane voltage drop along the permeation pathway. Received: 11 April 2000/Revised: 17 October 2000  相似文献   

10.
Single inward rectifier K+ channels were studied in Xenopus laevis embryonic myocytes. We have characterized in detail the channel which is most frequently observed (Kir) although we routinely observe three other smaller current levels with the properties of inward rectifier K+ channels (Kir(0.3), Kir(0.5) and Kir(0.7)). For Kir, slope conductances of inward currents were 10.3, 20.3, and 27.9 pS, in 60, 120 and 200 mM [K+] o respectively. Extracellular Ba2+ blocked the normally high channel activity in a concentration-dependent manner (K A = 7.8 μm, −90 mV). In whole-cell recordings of inward rectifier K+ current, marked voltage dependence of Ba2+ block over the physiological range of potentials was observed. We also examined current rectification. Following step depolarizations to voltages positive to E K , outward currents through Kir channels were not observed even when the cytoplasmic face of excised patches were exposed to Mg2+-free solution at pH 9.1. This was probably also true for Kir(0.3), Kir(0.5) and Kir(0.7) channels. We then examined the possibility of modulation of Kir channel activity and found neither ATP nor GTP-γS had any effect on Kir channel activity when added to the solution perfusing the cytoplasmic face of a patch. Kinetic analysis revealed Kir channels with a single open state (mean dwell time 72 msec) and two closed states (time constants 1.4, 79 msec). These results suggest that the native Kir channels of Xenopus myocytes have similar properties to the cloned strong inward rectifier K+ channels, in terms of conductance, kinetics and barium block but does show some differences in the effects of modulators of channel activity. Furthermore, skeletal muscle may contain either different inward rectifier channels or a single-channel type which can exist in stable subconductance states. Received: 16 September 1996/Revised: 14 March 1997  相似文献   

11.
Opening of ATP-sensitive K+ (KATP) channels by the uncoupler of oxidative phosphorylation, 2,4 dinitrophenol (DNP), has been assumed to be secondary to metabolic inhibition and reduced intracellular ATP levels. Herein, we present data which show that DNP (200 μm) can induce opening of cardiac KATP channels, under whole-cell and inside-out conditions, despite millimolar concentrations of ATP (1–2.5 mm). DNP-induced currents had a single channel conductance (71 pS), inward rectification, reversal potential, and intraburst kinetic properties (open time constant, τopen: 4.8 msec; fast closed time constant, τclosed(f): 0.33 msec) characteristic of KATP channels suggesting that DNP did not affect the pore region of the channel, but may have altered the functional coupling of the ATP-dependent channel gating. A DNP analogue, with the pH-titrable hydroxyl replaced by a methyl group, could not open KATP channels. The pH-dependence of the effect of DNP on channel opening under whole-cell, cell-attached, and inside-out conditions suggested that transfer of protonated DNP across the sarcolemma is essential for activation of KATP channels in the presence of ATP. We conclude that the use of DNP for metabolic stress-induced KATP channel opening should be reevaluated. Received: 10 September 1996/Revised: 27 December 1996  相似文献   

12.
目的探讨建立急性心功能不全动物模型的可行性。方法完全结扎犬前降支,进行快速右室起搏,使心输出量(CCO)较基础状态稳定地下降50%,分别测定基础及心输出量下降状态下的血压(AP)、血氧(SaO2)、平均右房压(mRAP)、平均肺毛压(mPCWP)、系统血管阻力(SVR)、心腔大小、左室射血分数(LVEF)、血浆肾素活性(PRA)、内皮素(ET)、尿量(UO)、血肌酐(Scr)、肌酐清除率(Ccr)。结果结扎LAD和快速右室起搏后,CCO较基础状态均稳定地下降50%,CCO降低后,AP、SaO2显著下降,mRAP、mPCWP、SVR显著升高;心脏各腔室明显扩大,LVEF显著降低;PRA、ET、Scr明显升高,UO、Ccr明显下降。结论结扎冠状动脉前降支及快速右心室起搏可成功制作急性心功能不全的动物模型。  相似文献   

13.
杨建忠  欧柏青  骆扬平 《生物磁学》2009,(13):2511-2513
目的:探讨辛伐他汀对早期急性冠状动脉综合症患者血浆及vWF水平的影响。方法:将120例性冠状动脉综合症患者随机分为常规治疗组(60例)与辛伐他汀治疗组(60例),常规治疗组采用拜阿司匹林、硝酸酯类、血管紧张素转换酶抑制剂等,辛伐他汀组在常规治疗基础上加用辛伐他汀;疗程8周。检测患者治疗前后的hs-CRP、LDL-C、HDL-C、TC、TG与vWF等因子水平的变化。选取60例健康人作为对照组。结果:常规治疗组中患者的hs-CRP、TC与vWF的水平明显下降(P〈0.05);辛伐他汀组中患者的hs-CRP、LDL-C、TC、TG与vWF的水平明显下降(P〈0.01)、而HDL-C的水平明显升高(P〈0.05)。与常规治疗组相比,辛伐他汀组中患者的hs-CRP、LDL-C、TG与vWF的的水平变化差异均有统计学意义(P〈0.05)。结论:常规药物联合辛伐他汀治疗早期急性冠状动脉综合症可获得较好的疗效。  相似文献   

14.

Objectives

Patients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development.

Methods

We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.

Results

73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development.

Conclusion

The presence of CE was associated with poorer coronary collateral development in patients with SCAD.  相似文献   

15.
本文探讨依靠RNAi技术对猪繁殖与呼吸综合征病毒(PRRSV)增殖的干扰作用。筛选到针对编码PRRS病毒核衣壳蛋白的N基因的两处靶序列作为候选片段,在MARC-145细胞上进行基因干扰实验研究。成功观测到由载体表达的小干扰RNA(siRNA)在MARC-145细胞中对PRRS病毒增殖的抑制现象。通过选取不同时间段对病毒进行TCID50检测,以及对CPE出现时间进行观察和免疫荧光技术,得到RNA干扰对PRRS病毒增殖抑制作用的动态数据。证实在真核细胞水平上,RNA干扰机制可以抑制PRRS病毒的增殖。实验结果表明,依靠载体表达的RNA干扰技术将会对今后针对PRRS病毒的新型疫苗开发提供一个新思路。  相似文献   

16.
17.
This study aims to analyze the clinical significance of the measuring B-type natriuretic peptide (BNP) and stress glycemia in patients with acute coronary syndrome (ACS), and to investigate the relationships between the two biomarkers and the severity of coronary artery lesions. One hundred and five consecutive patients with ACS admitted for coronary artery angiography were divided into three clinical subgroups. These patients were then further assigned into either of three subgroups according to their Gensini score. Moreover, a group of patients with stable angina (SA) and those with no history of coronary disease served as controls. The patients’ BNP levels were analyzed on admission and their fasting blood glucose was measured the next morning. BNP and fasting blood glucose concentrations were highly elevated in patients with ACS irrespective of their subgroups compared to SA and control patients. This observation was statistically significant (P < 0.001). Further, the concentrations of BNP and fasting blood glucose between the three ACS subgroups were significantly different (P < 0.001) depending on the severity of the coronary artery disease. There is a positive correlation between levels of BNP and blood glucose concentration and Gensini score in ACS patients (r = 0.782, P < 0.05, r = 0.732, P < 0.05). BNP level and stress glycemia were significantly higher in ACS patients than those in SA and control groups. There is a correlation between BNP level and stress blood glucose concentration and the severity of coronary artery lesions. Combined analysis of BNP and stress blood glucose can be helpful and effective for risk stratification of patients with ACS after admission.  相似文献   

18.
We investigated the block of KATP channels by glibenclamide in inside-out membrane patches of rat flexor digitorum brevis muscle. (1) We found that glibenclamide inhibited KATP channels with an apparent K i of 63 nm and a Hill coefficient of 0.85. The inhibition of KATP channels by glibenclamide was unaffected by internal Mg2+. (2) Glibenclamide altered all kinetic parameters measured; mean open time and burst length were reduced, whereas mean closed time was increased. (3) By making the assumption that binding of glibenclamide to the sulphonylurea receptor (SUR) leads to channel closure, we have used the relation between mean open time, glibenclamide concentration and K D to estimate binding and unbinding rate constants. We found an apparent rate constant for glibenclamide binding of 9.9 × 107 m −1 sec−1 and an unbinding rate of 6.26 sec−1. (4) Glibenclamide is a lipophilic molecule and is likely to act on sulfonylurea receptors from within the hydrophobic phase of the cell membrane. The glibenclamide concentration within this phase will be greater than that in the aqueous solution and we have taken this into account to estimate a true binding rate constant of 1.66 × 106 m −1 sec−1. Received: 7 July 1996/Revised: 4 October 1996  相似文献   

19.
Coronary angiography allows a direct evaluation of coronary anatomy. The aim of the present investigation was to search for correlations between the magnitude of coronary artery disease, as assessed by angiography, and a number of systemic parameters. A group of 116 patients (80 male, 36 female) with coronary heart disease diagnosed by angiography, aged 62.0±10.5 years, was the subject of an observational study. Correlation and linear regression analysis using coronary artery disease burden (CADB - sum of the percentage of the luminal stenosis encountered in all the lesions of the coronary arterial trees) as dependent variable, and age, sex, plasma calcium, phosphorus, magnesium, glucose, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, estimated glomerular filtration rate and body mass index as independent variables, were carried out. Significant correlation values versus CADB were seen with age (r 0.19, p 0.04), uric acid (r 0.18, p 0.048) and fasting plasma glucose (r 0.33, p<0.001). Linear regression analysis, yielding a global significance level of 0.002, showed a significant value for glucose (p 0.018) and for sex (0.008). In conclusion, among several systemic parameters studied, plasma glucose was found to be correlated to coronary artery atherosclerosis lesions.  相似文献   

20.
Data obtained with the lipid bilayer technique indicate that cis (cytoplasmic) concentration of 4.4–22 mm hydrogen peroxide (H2O2), is a water-soluble oxidant. [H2O2] cis (n= 26) reversibly inhibits the multisubconductance SCl channel of the sarcoplasmic reticulum vesicles from rabbit skeletal muscle. At −40 mV, the mean values of the current amplitude (I) and the probability of the SCl channel being open (P o ) were reduced significantly (n= 8) from −6.14 ± 0.42 pA and 0.69 ± 0.06 (for all conductance levels) in control 0.0 mm [H2O2] cis to −1.10 ± 0.51 pA and 0.13 ± 0.04 (for the intermediate subconductance states) in 8.8 mm [H2O2] cis , respectively. The [H2O2] cis -induced decrease in P o is mainly due to a decrease in the mean open time T o . The mechanism of [H2O2] cis effects on the multiconductance SCl channel is characterized by a mode shift in the channel state from the main conductance state to the low subconductance states. The estimated concentration of the [H2O2] cis for the half inhibitory constant, K i , was 11.78 mm, higher than the estimated 8.0 and 8.1 mm for the parameters P o and T o , respectively, indicating that the conductance of the SCl channel is less sensitive than the gating kinetics of the channel. After a lag period of between 30 to 60 sec, the lipophilic SH-oxidizing agent 4,4′-dithiodipyridine (4,4′-DTDP) added to the cis side at 1.0 mm removed the inhibitory effects of 8.8 mm [H2O2] cis . The 4,4′-DTDP-enhanced SCl channel activity was blocked after the addition of 0.5 mm ATP to the cis side of the channel. The addition of 1.0 mm 4,4′-DTDP to the cis or trans solutions facing an SCl channel already subjected to 0.5 mm [ATP] cis or [ATP] trans failed to activate the ATP-inhibited SCl channel. These findings suggest that 4,4′-DTDP is not preventing the binding of ATP to its binding site on the channel protein. The interaction of H2O2 with the SCl channel proteins is consistent with a thiol-disulfide redox state model for regulating ion transport, where SH groups can directly modify the function of the channel and/or the availability of regulatory sites on the channel proteins. The H2O2 effects on the Ca2+ countercurrent through the SCl channel are also consistent with H2O2-modification of the mechanisms involved in the Ca2+ regulation, which underlies excitation-contraction coupling in skeletal muscle. Received: 27 April 1999/Revised: 1 July 1999  相似文献   

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