心脏牵张激活性离子通道的研究进展

心脏受到机械刺激时，会引起心肌细胞膜电活动的改变而导致心律失常，牵张激活性离子通道在其中扮演了重要角色。本文综述了心脏牵张激活性离子通道的特性及其与心律失常关联性的研究成果和进展，并对该领域研究前景进行展望。     

心脏机械-电反馈研究进展

心脏是一个复杂的应力感受系统。心脏应力变化对自身电活动的影响 (主要是指直接影响 )被称为心脏机械 -电反馈(MEF)。牵张敏感离子通道可能是心脏MEF过程中重要的信号转导分子 ,在心肌已发现两类牵张激活的阳离子通道。研究MEF的发生机理以及心肌牵张敏感阳离子通道的特性 ,将可能为心律失常的防治开辟新的领域。     

心肌离子通道的研究进展

心血管疾病主要死因是致命性心律失常,对它的治疗仍是一个问题。心肌细胞膜上存在多种离子通道,这些通道表达和功能的彼此平衡是心脏正常功能的基础。当某种通道的功能或表达异常时,通道间平衡被打破,将出现心律失常。对心肌离子通道的全面认识,可以从分子水平更好的解释心肌电生理及病理机制。     

心肌离子通道与抗心律失常药研究进展

自 1990年提出西西里方案以来 ,运用膜片钳技术 (patchclamptechnique)研究心律失常机制已是国际公认的方法 ,从基因分子水平研究心律失常及多角度、多元化研究开发抗心律失常药已成为新的趋势 ,本文阐述近年来心肌离子通道研究现状及抗心律失常药的研究进展 ,为新药研究开发和临床应用提供理论依据。     

心肌细胞离子通道的研究进展

心肌细胞膜上的离子通道类型多,性质复杂。各通道的分子结构、电导值、门控动力学特性、离子动力学特性、通道的特异性激动剂及阻滞剂各不相同,在动作电位的形成中起到各自的作用。心脏主要的离子通道包括钙离子、钾离子、钠离子及近年发现的氯离子通道。膜片钳技术和分子生物学的深入研究,认识到离子通道对维持心脏生理状态起到重要作用,而在心脏疾病时,其活性及功能发生变化。对心脏离子通道的全面认识,可以从分子水平更好地解释心脏电生理及病理机制。     

细胞骨架对心肌离子通道活动的影响

微管、微丝、中间丝及其结合蛋白构成心肌细胞的骨架系统,它们对于维持心肌细胞正常形态、调节心肌细胞一系列生理活动有重要作用。本文从骨架蛋白对心肌离子通道活动的影响,对目前国内外研究现状进行综述,认为进一步研究心肌细胞骨架、骨架蛋白与心肌离子通道的相互关系,有十分重要的意义。     

心肌除复极的非同步与心律失常

<正>心律失常的发生原理分为冲动起源和传导异常及两者相结合。这种按生理模式分类虽合乎情理且易于理解,但难于从微观角度理解心肌电紊乱。因心肌电本质是微观离子流动的结果,部分复杂心律失常多发生于微小区域内,特别是恶性心律失常~〔1〕;且严重心肌电紊乱时,心脏异质性增大,心肌传导功能的下降和有效不应期的非一致性为心律失常的发生提供了基础。而心肌动作电位时程(APD)包括除极和复极,两者本为密切联系,序贯进行的过程,但在特定条件下邻近细胞间却相     

心律失常的心肌电生理研究进展

本文着重综述了心脏起搏功能的变化、触发活动和折返激动方面的研究进展     

巨噬细胞调控离子通道致心律失常研究的最新进展

传统观点认为心律失常的发生机制主要与离子通道电流有关,近年来研究发现心脏中固有巨噬细胞和血液单核细胞分化而来的巨噬细胞,可通过调节ICa,T等离子通道影响离子电流,从而在心脏正常电传导中发挥作用,并与房性、室性心律失常密切相关.这为心律失常的治疗提供了新的思路.     

机械敏感性离子通道Piezo1在循环系统疾病中的研究进展

Piezo1通道是一种非选择性阳离子机械敏感性离子通道,主要表达于非兴奋细胞中,是多种生理过程不可或缺的部分。Piezo1通道结构和功能异常可导致多种疾病病理生理过程,如淋巴水肿、主动脉瓣二叶瓣、胚胎血管重构缺陷等。本文将从心脏、血管、淋巴系统三方面综述Piezo1与循环系统疾病的研究进展。     

心脏黏液瘤的遗传学研究进展

黏液瘤是最常见的心脏原发良性肿瘤,但发病隐匿,有复发及家族遗传倾向,临床上易出现系统性栓塞、猝死等。目前关于心脏黏液瘤的遗传学发病机制尚不清楚。本文对近年黏液瘤遗传学研究进展予以综述,为心脏黏液瘤的综合认识及诊治提供依据。     

心脏记忆及其机制的研究进展

心脏记忆作为一种心脏电生理重构现象主要表现为心脏在出现异位兴奋如心室起搏、预激综合征或者室性心动过速后产生T波方向的改变,并在恢复窦性心律后仍持续一段时间。但其产生的分子机制仍未被完全研究和阐述清楚,且其在不同阶段所涉及的信号转导途径也各不相同。目前的研究认为心脏记忆的产生主要和心肌细胞表面与复极相关的离子通道表达下调,缝隙连接重构有关。这一过程由心脏机械电反馈机制触发,受血管紧张素Ⅱ和环磷腺苷反应元件结合蛋白的调节。现主要介绍心脏记忆现象的特点及其电生理重构机制的最新研究进展。     

心脏再生治疗的最新进展

心肌梗死等原因导致心脏损伤后,受损的心肌细胞被纤维组织所取代并导致心脏泵功能损伤,最终进展为心力衰竭。目前,心肌梗死等心血管疾病的治疗重点是防止进展为心力衰竭,而终末期心力衰竭患者只能通过心脏移植才能存活。近几十年来众多科学家一直坚持不懈地追求修复受损心脏和改善心脏功能的方法。本文主要综述了心脏再生治疗的最新研究进展、局限性和发展前景。     

Physiological Modulation of Cardiac Gap Junction Channels

Cardiac Gap Junction Channel Regulation. Synchronization of pacemaker activity and cardiac action potential propagation is dependent upon the maintenance of electrical communication via gap junctions. Gap junction channels in mammalian heart are formed by a 43-kilodalton (kD) protein, connexin43, and have a unitary conductance of 50 picosiemens (pS). In embryonic chick heart, three gap junction proteins of 42, 43, and 45 kD have been cloned, the functional properties of which have not been individually identified. Unitary channel conductances ranging from 40-240 pS have been reported, but conductances of 40-80 and 160 pS are most frequently observed in embryonic chick heart. Developmental changes in transjunctional voltage dependence are known to occur and may be correlated with differential expression of the three chick connexins during development. Gap junction conductance (g_j) is highly regulated, being maintained or increased by ATP and cAMP-dependent pathways. Conversely, g_j is reduced by treatment with various lipophilic agents (e.g., n-alkanols, arachidonic acid, halothane), large transjunctional potentials, increasing intracellular cation (e.g., H⁺, Ca²⁺) concentrations, and tyrosine phophorylation of rat connexin43. It is unclear at this time if any of the regulatory mechanisms can mediate beat-to-beat fluctuations in g_j of normal myocardium. Most available evidence indicates that this modulation occurs by the open-closed gating of individual channels rather than effects on the unitary channel conductance. The precise molecular mechanisms are not yet known, but the functional expression of gap junction proteins should allow for determination of the functional domains responsible for direct and indirect modulation of the cardiac gap junction proteins.     

Autonomic Regulation of Voltage-Gated Cardiac Ion Channels

Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na_V1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by β adrenergically stimulated G-proteins. We demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na_V1.5, Ca_V1.2a, and K_V1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.     

Calcium Channels in Cardiac Hypertrophy and Heart Failure

With the development of cardiac hypertrophy and heart failure, there are profound alterations in the ability of the cardiac cell to contract and relax. Despite several decades of intensive investigation, the precise cellular mechanisms responsible for this contractile dysfunction remain unknown. Recent advances in confocal microscopy and fluorescent calcium (Ca⊃2⊃+) indicators have allowed investigators to image the focal release of Ca⊃2⊃+ from the sarcoplasmic reticulum for the first time. The use of these techniques offers the unique opportunity to study the elemental events of excitation&ndash;contraction coupling in diseased myocardium. In this review, we focus on the role of calcium channels (L-type and T-type) and the TTX-sensitive Ca⊃2⊃+-permeable sodium (Na⊃+) channel in normal and abnormal cardiac function. Additionally, the role of the sodium&ndash;calcium exchanger and the voltage-activated process in cardiac excitation&ndash;contraction coupling is discussed. The application of newer microscopic techniques to study animal models that mimic human disease longitudinally will provide the means to identify precisely the abnormalities in calcium handling that occur with the development of cardiac hypertrophy and heart failure. This revised version was published online in July 2006 with corrections to the Cover Date.     

Structure and Neural Modulation of Cardiac Calcium Channels

Regulation of Cardiac Ca Channels . The L-type, voltage-gated calcium (Ca) current plays a key role in excitation and initiation of contraction in cardiac muscle cells and is partly responsible for the plateau of the action potential. The ionic channels underlying this current are targets for modulation by the autonomic nervous system. This article reviews recent developments in understanding how these channels are regulated by phosphorylation and G proteins and attempts to relate these findings to recent studies on the molecular structure of the Ca channel.     

干细胞移植用于心脏起搏的研究进展

电子起搏器治疗窦房结功能障碍及其它心脏传导系统疾病已获得较好的效果,但也伴随一些负面效应:高费用、有限的电池寿命及缺乏对神经激素生理性反应等。细胞移植是一项快速发展的治疗方法,其中干细胞移植在心脏起搏方面的基础研究获得了突破性的进展,现就此作一综述。