Mechanism of Thyrotoxic Periodic Paralysis
Mechanism of Thyrotoxic Periodic Paralysis
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DOI：
10.1681/asn.2012010046
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发表时间：
2012-06-01
影响因子：
13.6
通讯作者：
Huang, Chou-Long
中科院分区：
文献类型：
--
作者：
Lin, Shih-Hua;Huang, Chou-Long
甲亢性周期性麻痹的发病机制一直被认为与甲状腺激素和/或肾上腺素能亢进和高胰岛素血症刺激的Na+-K+ ATP酶活性增加有关。然而，仅此机制不能充分解释急性发作期间低钾血症的发生或相关的静息膜电位的反常去极化。最近的研究发现，骨骼肌特异性内向整流K+（Kir）通道Kir2.6的功能突变与甲状腺毒性周期性麻痹相关，这为骨骼肌外向K+流出减少提供了新的见解，无论是通道突变还是激素抑制（肾上腺素或胰岛素），可导致低钾血症和反常去极化的恶性循环，这反过来，使Na+通道失活并导致肌肉不兴奋和瘫痪。
The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na+-K+ ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. This mechanism alone, however, cannot adequately explain how hypokalemia occurs during acute attacks or the associated paradoxical depolarization of the resting membrane potential. Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K+ (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K+ efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na+ channels and causes muscle unexcitability and paralysis.