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首页> 外文会议>Southern Biomedical Engineering Conference >Respiratory Abnormalities in the Kcna1-Null Mouse Model of Sudden Unexpected Death in Epilepsy
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Respiratory Abnormalities in the Kcna1-Null Mouse Model of Sudden Unexpected Death in Epilepsy

机译：癫痫猝死意外的Kcna1空小鼠模型中的呼吸异常

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Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in young and otherwise healthy patients with epilepsy, and sudden unexpected death is at least 20 times more common in epilepsy patients than the general population. Cardiac arrhythmias, respiratory abnormalities, or a combination of both have been postulated in the causation of SUDEP. Voltage-gated Kv1.1 channels, encoded by the Kcna1 gene, conduct a critical potassium current in neurons that prevents hyper excitability. Mice lacking the Kcna1 gene recapitulate critical aspects of SUDEP, including frequent generalized seizures, autonomic instability, cardiac dysfunction, and premature death, but seizure-related respiratory dysfunction has never been investigated. Here, we used unrestrained whole body plethysmography recordings of conscious, unanesthetized mice to test the hypothesis that Kcna1-null mice exhibit seizure-related respiratory abnormalities that predispose the animals to SUDEP. In baseline measurements of respiratory function, we found that null animals exhibited similar breathing rates, tidal volumes, and minute volumes compared to wild type littermate controls. However, null mice exhibited an 85% reduction in apnea frequency suggesting the Kcna1 gene may be important for basal respiratory physiology. Specifically, Kcna1-null mice showed a drastic reduction in the number of type 1 post-sigh apneas despite exhibiting a normal incidence of sighs. In addition, during seizures, null mice exhibited malignant respiratory abnormalities characterized by a pattern of hyperpnea transitioning to intermittent ataxic or apneic breathing, depending on seizure severity. This seizure-related respiratory impairment could potentially exacerbate or evoke ictal cardiac arrhythmias and predispose the animals to SUDEP. Future work will define the sequence of respiratory and cardiac events during seizures in these mice to determine whether respiratory dysfunction occurs primary or sec- ndary to arrhythmias.
机译：癫痫猝死（SUDEP）是年轻和其他健康的癫痫患者与癫痫相关的死亡的主要原因，癫痫患者的突然猝死是普通人群的至少20倍。 SUDEP的病因被假定为心律不齐，呼吸异常或两者兼而有之。由Kcna1基因编码的电压门控Kv1.1通道在神经元中传导关键的钾电流，从而阻止了过度兴奋性。缺乏Kcna1基因的小鼠概括了SUDEP的关键方面，包括频繁的全身性癫痫发作，自主神经不稳定，心脏功能障碍和过早死亡，但从未研究过癫痫发作相关的呼吸功能障碍。在这里，我们使用了有意识的，没有麻醉的小鼠的不受约束的全身体积描记记录，以检验Kcna1无效小鼠表现出癫痫发作相关的呼吸异常的假说，使动物易患SUDEP。在呼吸功能的基线测量中，我们发现与野生型同窝仔对照相比，空动物表现出相似的呼吸速率，潮气量和分钟气量。但是，空小鼠的呼吸暂停频率降低了85％，这表明Kcna1基因可能对基础呼吸生理很重要。具体地说，尽管表现出正常的叹息现象，但Kcna1无效的小鼠仍表现出1型叹气后呼吸暂停次数的急剧减少。另外，在癫痫发作期间，视癫痫发作的严重程度而定，空小鼠表现出恶性呼吸异常，其特征在于呼吸过度转变为间歇性共济失调或呼吸暂停呼吸。这种与癫痫发作有关的呼吸系统损害可能会加重或诱发发作性心律失常，并使动物容易发生SUDEP。未来的工作将确定这些小鼠癫痫发作期间呼吸和心脏事件的顺序，以确定呼吸功能障碍是发生于心律不齐的原发还是继发于心律失常。

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