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: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821463
• 关键词: action potentials; arrhythmia; calcium metabolism; heart cell; heart contraction; heart disorder diagnosis; heart metabolism; heart rhythm; imaging /visualization /scanning; ion transport; muscle tone; myofibrils; sarcolemma; sarcomeres; sarcoplasmic reticulum; tissue /cell culture

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.

所有哺乳动物心脏准备，给予充足的Ca 2 + 负载，表现出自发释放的Ca 2+从 肌浆网（SR）。 视频显微镜在肌肉和 肌细胞已经表明，由于这种类型的肌丝运动， 的Ca 2+释放是（1）空间不均匀和（2）传播在 约100 μ m sec作为收缩波，表明 自发的Ca 2+释放发生在局部，并且在扩散中， 沿其浓度梯度下降，导致再生Ca 2 + 诱导SR中Ca ~（2+）释放。 作为自发SR释放的结果，估计范围为 从几微米到40微米。 高钙区的肌丝 缩短和拉伸邻近肌丝，其中（Ca 2+） 低于 因为，在大块心脏组织中， 在细胞之间，静止的细胞被拉伸， 这些细胞中的肌节负载受到影响。 的净结果 这些事件是Ca 2+依赖性舒张张力。 舒张 肌膜离子电导的振荡Ca ~（2+）调节 在高Cai区域内导致肌膜去极化， 如果强度足够的话，会引发一种自发的行为 可能导致心律失常。 最后，结果 电位的不均匀性和心律失常。 最后， SR Ca 2+负载程度的不均匀性， SR Ca 2+再循环的阶段，发生在存在 自发SR Ca 2+释放导致净范围减少 收缩期Ca 2+从SR释放的同步性 后续动作电位。 这会损害收缩功能。 舒张张力增强，心律失常的发生，以及 收缩功能受损是许多心脏病的主要标志 心肌疾病状态。 自发性的概念化 SR Ca 2+释放，如在本文中解释和讨论的 目前的研究结果在心肌细胞，虽然投机是一些 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的潜在作用的可检验假设 心脏病的症状