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PATHOPHYSIOLOGIC EFFECTS OF SPONTANEOUS CA2+ RELEASE IN THE HEART

PATHOPHYSIOLOGIC EFFECTS OF SPONTANEOUS CA2+ RELEASE IN THE HEART
心脏自发 CA2 释放的病理生理学影响
批准号:
3821463
负责人:
M C CAPOGROSSI
金额:
$0.0万
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依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
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中文摘要
翻译
所有哺乳动物心脏制剂,给予足够的钙 负荷,表现出自发性的钙释放 肌浆网(SR)。肌肉和肌肉中的视频显微镜 肌细胞已经表明,由于这种类型的肌丝运动 的钙释放是(1)空间不均匀的,(2)在 大约100微米秒作为收缩波,表明 自发的钙释放发生在局部,并在扩散中 向下其浓度梯度,导致再生的钙离子 诱导肌浆网钙释放。实现的本地化(钙) 由于SR自发释放的结果估计在 高钙区肌丝数微米至40微米 缩短和拉伸邻近的肌丝,其中(钙是 再低一点。因为在大块心脏组织中,这是异步发生的 在细胞之间,静止的细胞被拉伸,因此 这些细胞中的肌节负荷受到影响。最终的结果是 这些事件是钙依赖的舒张压。舒张期 钙离子对肌膜离子电导的振荡调节 在高CaI的区域内导致肌膜去极化, 如果规模足够大,就会触发自发的行动 并导致心律失常。最后,由此产生的 对心律失常的电位和LAD的不均一性。最后, 由此产生的肌浆网钙负荷和肌浆网钙负荷的不均一性 在存在的情况下,SR钙循环的阶段 自发的肌浆网钙释放导致净范围的减少 从SR释放的收缩期钙的同步性 后续动作电位。这会损害心脏的收缩功能。 舒张压增强,心律失常的发生,以及 收缩功能受损是许多 心肌疾病状态。自发性的概念化 SR钙释放,在 目前在心肌细胞中的发现,尽管是推测的一些 在这方面,提供了一个逻辑框架,其中没有结构 关于其在病理生理学中潜在作用的可检验假说 某些形式的心脏病。
英文摘要
All mammalian cardiac preparation, given sufficient Ca2+ loading, exhibit spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR). Videomicroscopy in muscle and myocytes has shown that the myofilament motion due to this type of Ca2+ release is (1) spatially non-uniform and (2) propagates at approximately 100 um sec as a contractile wave, indicating that the spontaneous Ca2+ release occurs locally, and, in diffusing down its concentration gradient, cause a regenerative Ca2+ induced Ca2+ release from the SR. The localized (Ca2+) achieved as result of spontaneous SR release has been estimated to range from a few um to 40 mu M. Myofilaments in areas of high Ca2+ shorten and stretch neighboring myofilaments where (Ca2+ is lower. Since, in bulk cardiac tissue this occurs asynchronously among cells, quiescent cells are stretched and therefore sarcomere loading in these cells is affected. The net result of these events is Ca2+-dependent diastolic tonus. The diastolic oscillatory Ca2+ modulation of sarcolemmal ion conductances within areas of high Cai results in sarcolemmal depolarization, which, if sufficient in magnitude, triggers a spontaneous action potential and leads to arrhythmias. Finally, the resultant inhomogeneity in the potential and lads to arrhythmias. Finally, the resultant inhomogeneity in the extent of SR Ca2+ loading and phases of SR Ca2+ recycling that occur in the presence of spontaneous SR Ca2+ release cause a reduction in the net extent and synchrony of systolic Ca2+ release from the SR by a subsequent action potential. This impairs systolic function. Enhanced diastolic tone, the occurrence of arrhythmias, and compromised systolic function are cardinal signs of many myocardial disease states. The conceptualization of spontaneous SR Ca2+ release as interpreted and discussed in the context of the present findings in cardiac myocytes, though speculative is some regard, provides a logical framework in which no structure testable hypotheses about its potential role in the pathophysiology of some forms of heart disease.
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EFFECT OF ALPHA-ADRENERGIC STIMULATION ON ISOLATED VENTRICULAR MYOCYTES
  • 批准号:
    3817601
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    M C CAPOGROSSI
  • 依托单位:
GENE THERAPY OF CORONARY ARTERY DISEASE
  • 批准号:
    3745552
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    M C CAPOGROSSI
  • 依托单位:
MECHANISMS OF ABNORMAL AUTOMATICITY IN CARDIAC PREPARATIONS
  • 批准号:
    3821461
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    M C CAPOGROSSI
  • 依托单位:
GENE THERAPY TO INDUCE THERAPEUTIC ANGIOGENESIS
  • 批准号:
    2565760
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    M C CAPOGROSSI
  • 依托单位:
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