ACUTE QUADRIPLEGIC MYOPATHY

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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.