MRC Centre for Neuromuscular Diseases, Queen Square, Institute of Neurology, UCL, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Department of Neurology and Neurophysiology, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust and Department of Academic Neurosciences, Kings College London, UK.
MRC Centre for Neuromuscular Diseases, Queen Square, Institute of Neurology, UCL, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Clin Neurophysiol. 2020 Apr;131(4):816-827. doi: 10.1016/j.clinph.2019.12.414. Epub 2020 Jan 27.
Hypokalaemic periodic paralysis (HypoPP) is caused by mutations of Ca1.1, and Na1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Na1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo.
MVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP(n = 7), HypoPP (n = 10), and normal controls (n = 26).
Muscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges.
The in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita.
MVRCs provide important in vivo data that complements expression studies of ion channel mutations.
低钾周期性瘫痪（HypoPP）是由 Ca1.1 和 Na1.4 的突变引起的，导致异常的门控孔电流。高钾周期性瘫痪（HyperPP）是由于 Na1.4 的主要α孔的功能获得性突变引起的。本研究使用肌肉速度恢复循环（MVRCs）来研究体内发作间期肌肉膜性质的变化。
在胫骨前肌中记录 MVRCs 和对刺激串的反应，并在 HyperPP（n=7）、HypoPP（n=10）和正常对照组（n=26）中进行比较。
HypoPP 中的肌肉相对不应期延长，发作间期静息膜电位去极化导致早期超极化减少。在 HyperPP 中，多次条件刺激的平均超极化和残留超极化增加，与内向钠电流增加和复极化延迟一致，易发生自发性肌强直性放电。
体内发现提示 HypoPP 中的发作间期静息膜电位去极化，而 HyperPP 中的静息膜电位大多正常。HyperPP 中的 MVRC 发现与窗电流一致，这是先前基于体外表达研究提出的。尽管临床上相似，但 HyperPP 在电生理上与先天性肌强直症不同。
MVRCs 提供了重要的体内数据，补充了离子通道突变的表达研究。
