DETERMINANTS OF EXTRAOCULAR MUSCLE FUNCTION

描述(摘自申请者摘要)：眼外肌(EOMS) 不是典型的骨骼肌。它们的解剖排列和纤维类型 异质性暗示着功能的多功能性，以及它们的收缩能力 特性呈现出在其他骨骼肌中不常见的特征。 EOMS的一个特征是存在两个纤维层：轨道，更接近 轨道；和全局，更接近眼球。每一层都有一个特定的 大量的纤维类型，可能在眼球运动中有特定的作用。在……里面 此外，EOMS的线粒体含量是所有哺乳动物骨骼中最高的 肌肉，可能是因为它们几乎不间断的活动。然而， 我们对EOMS的结构特征的了解比我们对这些特征的了解更多 转化为这个肌肉群的功能特性。功能界别 轨道层和全球层之间的差异以及线粒体的作用 在EOMS对游离囊液的瞬时调节中，钙离子尚未出现 已经被探索过了。该项目的中心假设是EOM 功能取决于不同的钙处理的区隔 离散肌层的特性和线粒体作为新的用途 胞浆内钙离子下沉。这一假设将通过实验加以验证 体外生理学和药理学研究 钙离子特异性荧光光谱分析。确定…的功能范围 EOMS和那些决定它们的细胞元素，我们将(1)检查 EOM的全球层和轨道层对CA2的处理能力；(2)分析 已鉴定的EOM纤维的动力学；以及(3)确定功能性 EOM发育异常的后果。拟议的实验是一项 建立决定细胞的细胞元素的初步方法 EOMS的功能特性。首先，现有证据表明， 两个EOM层的功能特性不同。第二，快速钙 EOMS的处理可能包括新颖地使用线粒体作为替代 CA2下沉。第三，视觉发育异常和EOM特异性中断 肌球蛋白的表达可能改变钙离子的收缩调节特性 EOMS。这个项目的结果将增加我们对 EOMS的生理学，并提供对这一肌肉群行为的洞察 在斜视等障碍中，以及他们对治疗的反应 干预措施。

DESCRIPTION (Adapted from Applicant's abstract): The extraocular muscles (EOMs) are not typical skeletal muscles. Their anatomical arrangement and fiber type heterogeneity are suggestive of functional versatility, and their contractile properties present characteristics not commonly seen in other skeletal muscles. A feature of EOMs is the presence of two fiber layers: orbital, closer to the orbit; and global, closer to the eyeball. Each layer has a particular population of fiber types and may have a specific role in eye movement. In addition, EOMs have the highest mitochondrial content of all mammalian skeletal muscles, probably as a consequence of their almost constant activity. However, we know more about the structural traits of the EOMS than we do about how these translate into the functional properties of this muscle group. The functional differences between the orbital and global layers, and the role of mitochondria in the instantaneous regulation of free cystolic Ca 2+ of EOMs have not yet been explored. The central hypothesis of this project proposes that EOM function depends on the compartmentalization of distinct Ca2+handling properties to discrete muscle layers and the use of mitochondria as novel cytosolic Ca2+ sinks. This hypothesis will be tested with experiments combining in vitro physiological and pharmacological studies with the use of Ca2+-specific fluorescence spectroscopy. To establish the functional limits of EOMs and those cellular elements that determine them, we will (1) examining the Ca2+ handling ability of global and orbital layers of EOM; (2) analyze the Ca2+ kinetics of identified EOM fibers; and (3) determine the functional consequences of abnormal EOM development. The proposed experiments are an initial approach to establishing the cellular elements that determine the functional properties of EOMs. First, available evidence suggests that the functional properties of the two EOM layers are different. Second, rapid Ca2+ handling by the EOMs may include the novel use of mitochondria as alternative Ca2+ sinks. Third, abnormal visual development and disrupted EOM-specific myosin expression may alter the contractile of Ca2+ handling characteristics of EOMs. The results from this project will increase our understanding of the physiology of EOMs, and provide insights into the behavior of this muscle group in disorders such as strabismus, and their response to therapeutic interventions.