Genotype and Phenotype Analysis of Patients With Sporadic Periodic Paralysis

Sung, Chih‐Chien; Cheng, Chih-Jen; Lo, Yi-Fen; Lin, Muh-Shi; Yang, Sung-Sen; Lin, Shih‐Hua; Hsu, Yu-Chuan

doi:10.1097/maj.0b013e31822b430c

Cited by 18 publications

(13 citation statements)

References 34 publications

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“…Paralysis episodes can be triggered by carbohydrate-rich meals, exercise, exposure to cold, fever, or emotional stress (Cannon, 2006; Sung et al, 2012). The current explanation for these paralysis attacks is that the resting membrane potential (V REST ) changes from −85 mV to −60 mV under hypokalemic conditions, leading to muscle fiber inexcitability (Rudel et al, 1984; Jurkat-Rott et al, 2009).…”

Section: Pathologies Linked To Gating Pore Currentsmentioning

confidence: 99%

Biophysics, pathophysiology, and pharmacology of ion channel gating pores

2014

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Voltage sensor domains (VSDs) are a feature of voltage gated ion channels (VGICs) and voltage sensitive proteins. They are composed of four transmembrane (TM) segments (S1–S4). Currents leaking through VSDs are called omega or gating pore currents. Gating pores are caused by mutations of the highly conserved positively charged amino acids in the S4 segment that disrupt interactions between the S4 segment and the gating charge transfer center (GCTC). The GCTC separates the intracellular and extracellular water crevices. The disruption of S4–GCTC interactions allows these crevices to communicate and create a fast activating and non-inactivating alternative cation-selective permeation pathway of low conductance, or a gating pore. Gating pore currents have recently been shown to cause periodic paralysis phenotypes. There is also increasing evidence that gating pores are linked to several other familial diseases. For example, gating pores in Nav1.5 and Kv7.2 channels may underlie mixed arrhythmias associated with dilated cardiomyopathy (DCM) phenotypes and peripheral nerve hyperexcitability (PNH), respectively. There is little evidence for the existence of gating pore blockers. Moreover, it is known that a number of toxins bind to the VSD of a specific domain of Na+ channels. These toxins may thus modulate gating pore currents. This focus on the VSD motif opens up a new area of research centered on developing molecules to treat a number of cell excitability disorders such as epilepsy, cardiac arrhythmias, and pain. The purpose of the present review is to summarize existing knowledge of the pathophysiology, biophysics, and pharmacology of gating pore currents and to serve as a guide for future studies aimed at improving our understanding of gating pores and their pathophysiological roles.

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Section: Pathologies Linked To Gating Pore Currentsmentioning

confidence: 99%

Biophysics, pathophysiology, and pharmacology of ion channel gating pores

2014

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“…Recently, a sporadic case of hypokalaemic periodic paralysis with Na V 1.4 mutation R1135H in the domain III voltage sensor was described (Sung et al , 2012). Until now, functional expression has not been published for this mutation.…”

Section: Introductionmentioning

confidence: 99%

NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery

Groome

Lehmann‐Horn

Fan

et al. 2014

Brain

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“…5,6 Due to often indistinguishable clinical features, we had shown previously that an assessment of urinary K þ excretion and blood acid-base status coupled with a detailed history and physical examination help separate the 2 groups. 7 Among the etiologies of hypokalemic periodic paralysis, the most common are thyrotoxic periodic paralysis [8][9][10][11][12][13] and sporadic periodic paralysis 14 in Asia and familial periodic paralysis in Western countries. 15,16 Within hypokalemic nonperiodic paralysis, the etiologies are complex and challenging to the clinician hoping to make an early diagnosis.…”

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confidence: 99%