Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure

Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of contraction and relaxation, and associated intracellular Ca²⁺ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary microembolizations. Comparisons were made with LV cardiomyocytes isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca²⁺ transients by fluo 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes exhibited an abnormal pattern of contraction and relaxation characterized by an attenuated initial twitch (spike) followed by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca²⁺ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation pattern and Ca²⁺ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action potential duration by administration of saxitoxin (100 nM) or lidocaine (30 μM) reduced the duration of the dome phase of both the contraction/relaxation profile as well as that of the Ca²⁺ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance of the spike-dome profile in the majority of HF cardiomyocytes. In HF cardiomyocytes, the action potential and Ca²⁺ transient duration were not significantly different from those measured in normal cells. However, the contraction-relaxation cycle was significantly longer in HF cells (314 ± 67 ms, n = 21, vs. 221 ± 38 ms, n = 46, mean ± SD), indicating impaired excitation-contraction uncou pling in HF cardiomyocytes. The results show that, in cardiomyocytes isolated from dogs with HF, contractile abnormalities and abnormalities of intracellular Ca²⁺ transients at low stimulation rates are characterized by a spike-dome configuration. This abnormal pattern appears to result from prolongation of the action potential. Received 22 January 1998; received after revision 16 March 1998; accepted 27 March 1998     

强拟凸域上的多项式主子模

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稀释水应用于匀浆辊流浆箱的数值模拟

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面内场对枝状畴形成的IID畴壁中VBL链的影响

实验研究了面内场作用下枝状畴形成的第2类哑铃畴(IID)畴壁中垂直布洛赫线(VBL)链的解体过程.发现存在一个与材料参量有关的临界面内场范围[H(0)ip对应IID畴壁中垂直布洛赫ip,H(1)ip],其中H(0)线链保持稳定的最大临界面内场,H(1)ip对应IID畴壁中垂直布洛赫线链完全解体的最小临界面内场.此外,实验发现不同低直流偏场下产生的枝状畴在面内场作用下的软化过程相同,且在这个临界面内场范围内畴壁中的VBL是逐步丢失的.同时实验结果也证明了枝状畴畴壁中VBL是随机分布的.     

基于模型参考自适应控制的穿孔轧机控制系统设计

对穿孔轧机速度控制系统进行模型的建立和简化,并针对轧制控制过程中参数变化等不确定性因素的影响,设计了基于波波夫超稳定理论的模型参考自适应控制方法,通过MATLAB仿真技术验证了该控制系统具有较好的动态控制性能和跟踪精度。     

基于知识图谱的我国农产品品牌研究述评

依据科学知识图谱相关理论，利用CiteSpace软件对农产品品牌相关文献进行可视化分析，再利用Netdraw软件描绘主要研究内容的网络关系，对我国农产品品牌研究的热点内容、演进历程和趋势进行分析.结果表明，农产品品牌研究内容主要集中在农产品品牌属性结构及效应、品牌评价、品牌建设运营及区域品牌/地理标志品牌等方面.研究内容的演进路径反映了不同阶段的研究特色，也契合了国家政策调整和经济社会发展需求变化.我国专注于农产品品牌研究的学者和机构较少，学者间或机构间也未建立起紧密的合作关系.未来研究应进一步完善农产品品牌基本理论及研究方法，拓展农产品品牌研究的深度与广度，建立合作紧密的学术研究网络.     

基于知识图谱的中国-东盟自由贸易区研究结构及热点分析

通过对国内中国-东盟自由贸易区研究已有文献的量化梳理,把握其研究结构特征和研究热点,以期为中国-东盟自由贸易区研究进一步深化提供参考依据。通过关键词共词分析以及社会网络分析、聚类分析、多维尺度分析等可视化分析方法对国内中国-东盟自由贸易区的研究现状进行了定量分析,分析结果显示,国内中国-东盟自由贸易区研究呈现4个热点,即区域经济一体化、争端解决机制、贸易效应、税收协调。     

New paradigms of CFTR chloride channel regulation

The Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel controls salt and water transport across epithelial tissues. Alterations in the activity of this ion channel lead to two major human diseases: cystic fibrosis (low CFTR activity) and secretory diarrhea (excessive CFTR activity). The goal of this article is to review recent developments in our understanding of two aspects of CFTR biology: (i) interactions between CFTR domains (intramolecular interactions) that control the gating of this epithelial chloride channel and (ii) interactions between CFTR and other proteins (intermolecular interactions) that couple the activity of this ion channel to additional cellular processes in epithelial cells (e.g. membrane traffic). Clarifying the nature of these interactions may lead to the development of novel strategies for treating diseases that involve the CFTR chloride channel. Received 12 October 1999; accepted 31 December 1999     

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