ACUTE QUADRIPLEGIC MYOPATHY

描述：（申请人摘要中的逐字记录）危重患者 急性四肢瘫痪性肌病（AQM）综合征， 肌肉的发育继发于纤维的电不兴奋性。我们以前的 研究表明，钠电流的减少可能是 不能在瘫痪的肌肉中产生动作电位。我们将使用松散 膜片钳直接研究受影响的纤维中的钠电流， 动物模型和受影响的患者，以确定是否异常钠 电流是瘫痪的原因我们将进行四组实验， 研究这种疾病的钠电流在第一组实验中，我们将 使用AQM的动物模型来确定动作电位的丧失是否 由于钠离子通道数量的减少或者钠离子通道是否 存在，但未正确打开。在第二组实验中， 将分别研究两种不同的钠离子通道， 受影响的肌肉我们的目标是确定这两种类型的钠 渠道受到影响，或者是否在一个或另一个的困难， 钠通道是问题的根源。在第三组实验中 使用计算机生成的动作电位模型来研究 调节肌肉纤维兴奋性的许多因素之间的联系。我们将 确定我们在我们的研究中发现的钠电流的异常是否 动物模型实验可以充分解释动作电位的丧失， 肌肉麻痹最后，我们将利用从研究中获得的知识， 动物模型，并确定为什么他们瘫痪。我们的长期目标是 确定为什么肌肉在这种综合症中会瘫痪， 一种治疗

DESCRIPTION: (Verbatim from the Applicant's Abstract) Critically ill patients develop a syndrome of acute quadriplegic myopathy (AQM) where paralysis of muscle develops secondary to electrical inexcitability of fibers. Our previous work suggests that a reduction in the sodium current may be the cause of inability to generate action potentials in paralyzed muscle. We will use loose patch clamp to directly study sodium current in affected fibers in both the animal model and affected patients to determine whether abnormalities of sodium current are the cause of paralysis. We will perform four sets of experiments to study sodium currents in this illness. In our first set of experiments we will use an animal model of AQM to determine whether loss of action potentials is due to a reduction in the number of sodium channels or whether sodium channels are present, but are not opening properly. In our second set of experiments we will study individually the two different sodium channels that are present in affected muscle. Our goal will be to determine whether both types of sodium channels are affected, or whether difficulties in one or the other of the sodium channels is the cause of the problem. In a third set of experiments will use a computer-generated model of action potentials to study interactions between the many factors that regulate excitability in muscle fibers. We will determine whether the abnormalities in sodium current that we have found in our animal model experiments can fully explain the loss of action potentials in paralyzed muscle. Finally, we will use knowledge gained from our studies of the animal model and determine why they are paralyzed. Our long-term goal is to determine why muscle becomes paralyzed in this syndrome so that we can develop a therapy.