scholarly journals An atypical CaV1.1 mutation reveals a common mechanism for hypokalemic periodic paralysis

2017 ◽  
Vol 149 (12) ◽  
pp. 1061-1064 ◽  
Author(s):  
Stephen C. Cannon
Keyword(s):  
Periodic Paralysis ◽  
Common Mechanism ◽  
Hypokalemic Periodic Paralysis ◽  
Inward Currents ◽  
New Evidence

Cannon reviews new evidence supporting a key role for anomalous inward currents in the etiology of hypokalemic periodic paralysis.

scholarly journals Na leak with gating pore properties in hypokalemic periodic paralysis V876E mutant muscle Ca channel

2017 ◽  
Vol 149 (12) ◽  
pp. 1139-1148 ◽  
Author(s):  
Clarisse Fuster ◽  
Jimmy Perrot ◽  
Christine Berthier ◽  
Vincent Jacquemond ◽  
Pierre Charnet ◽  
...  
Keyword(s):  
External Solution ◽  
Periodic Paralysis ◽  
Rate Of Change ◽  
Ca Channel ◽  
Leak Current ◽  
Hypokalemic Periodic Paralysis ◽  
Inward Currents ◽  
S3 Segment ◽  
Domain Iii ◽  
Pore Properties

Type 1 hypokalemic periodic paralysis (HypoPP1) is a poorly understood genetic neuromuscular disease characterized by episodic attacks of paralysis associated with low blood K+. The vast majority of HypoPP1 mutations involve the replacement of an arginine by a neutral residue in one of the S4 segments of the α1 subunit of the skeletal muscle voltage-gated Ca2+ channel, which is thought to generate a pathogenic gating pore current. The V876E HypoPP1 mutation has the peculiarity of being located in the S3 segment of domain III, rather than an S4 segment, raising the question of whether such a mutation induces a gating pore current. Here we successfully transfer cDNAs encoding GFP-tagged human wild-type (WT) and V876E HypoPP1 mutant α1 subunits into mouse muscles by electroporation. The expression profile of these WT and V876E channels shows a regular striated pattern, indicative of their localization in the t-tubule membrane. In addition, L-type Ca2+ current properties are the same in V876E and WT fibers. However, in the presence of an external solution containing low-Cl− and lacking Na+ and K+, V876E fibers display an elevated leak current at negative voltages that is increased by external acidification to a higher extent in V876E fibers, suggesting that the leak current is carried by H+ ions. However, in the presence of Tyrode’s solution, the rate of change in intracellular pH produced by external acidification was not significantly different in V876E and WT fibers. Simultaneous measurement of intracellular Na+ and current in response to Na+ readmission in the external solution reveals a rate of Na+ influx associated with an inward current, which are both significantly larger in V876E fibers. These data suggest that the V876E mutation generates a gating pore current that carries strong resting Na+ inward currents in physiological conditions that are likely responsible for the severe HypoPP1 symptoms associated with this mutation.

Morphologic alteration in the muscles of patients with hypokalemic periodic paralysis or myopathy

1990 ◽  
Vol 48 (3) ◽  
pp. 222-223
Author(s):  
T. Shimizu ◽  
Y. Muranaka ◽  
I. Ohta ◽  
N. Honda
Keyword(s):  
Clinical Manifestations ◽  
Quadriceps Muscle ◽  
Honeycomb Structure ◽  
Periodic Paralysis ◽  
Ultrastructural Changes ◽  
Hypokalemic Periodic Paralysis ◽  
Electron Microscopic ◽  
Tubular Aggregates ◽  
Hypokalemic Myopathy ◽  
Transmission Electron

There have been many reports on ultrastructural alterations in muscles of hypokalemic periodic paralysis (hpp) and hypokalemic myopathy(hm). It is stressed in those reports that tubular structures such as tubular aggregates are usually to be found in hpp as a characteristic feature, but not in hm. We analyzed the histological differences between hpp and hm, comparing their clinical manifestations and morphologic changes in muscles. Materials analyzed were biopsied muscles from 18 patients which showed muscular symptoms due to hypokalemia. The muscle specimens were obtained by means of biopsy from quadriceps muscle and fixed with 2% glutaraldehyde (pH 7.4) and analyzed by ordinary method and modified Golgimethod. The ultrathin section were examined in JEOL 200CX transmission electron microscopy.Electron microscopic examinations disclosed dilated t-system and terminal cistern of sarcoplasmic reticulum (SR)(Fig 1), and an unique structure like “sixad” was occasionally observed in some specimens (Fig 2). Tubular aggregates (Fig 3) and honeycomb structure (Fig 4) were also common characteristic structures in all cases. These ultrastructural changes were common in both the hypokalemic periodic paralysis and the hypokalemic myopathy, regardless of the time of biopsy or the duration of hypokalemia suffered.

ANAESTHESIA MANAGEMENT FOR A PATIENT WITH FAMILIAL HYPOKALEMIC PERIODIC PARALYSİS

2014 ◽  
Author(s):  
Özgül Keskin ◽  
Hatice Türe ◽  
Özge Köner ◽  
Ferdi Menda ◽  
Bora Aykaç
Keyword(s):  
Periodic Paralysis ◽  
Hypokalemic Periodic Paralysis

Hypokalemic periodic paralysis mutations: Confirmation of mutation and analysis of founder effect

1996 ◽  
Vol 6 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Christie L.S. Grosson ◽  
Jesus Esteban ◽  
Diane McKenna-Yasek ◽  
James F. Gusella ◽  
Robert H. Brown
Keyword(s):  
Founder Effect ◽  
Periodic Paralysis ◽  
Hypokalemic Periodic Paralysis

scholarly journals Identification and Functional Characterization of Kir2.6 Mutations Associated with Non-familial Hypokalemic Periodic Paralysis

2011 ◽  
Vol 286 (31) ◽  
pp. 27425-27435 ◽  
Author(s):  
Chih-Jen Cheng ◽  
Shih-Hua Lin ◽  
Yi-Fen Lo ◽  
Sung-Sen Yang ◽  
Yu-Juei Hsu ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Periodic Paralysis ◽  
Hypokalemic Periodic Paralysis

scholarly journals A Mutation in the KCNE3 Potassium Channel Gene Is Associated with Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis

2002 ◽  
Vol 87 (11) ◽  
pp. 4881-4884 ◽  
Author(s):  
Magnus R. Dias Da Silva ◽  
Janete M. Cerutti ◽  
Liliane A. T. Arnaldi ◽  
Rui M. B. Maciel
Keyword(s):  
Direct Sequencing ◽  
Genetic Defect ◽  
Sporadic Case ◽  
Ionic Channel ◽  
Periodic Paralysis ◽  
Resting Membrane Potential ◽  
Hypokalemic Periodic Paralysis ◽  
Dominant Disease ◽  
Periodic Paralyses ◽  
Thyrotoxic Hypokalemic Periodic Paralysis

Abstract Hypokalemic Periodic Paralyses comprise diverse diseases characterized by acute and reversible attacks of severe muscle weakness, associated with low serum potassium. The most common causes are Familial Hypokalemic Periodic Paralysis (FHypoKPP), an autosomal dominant disease, and Thyrotoxic Hypokalemic Periodic Paralysis (THypoKPP), secondary to thyrotoxicosis. Symptoms of paralysis are similar in both diseases, distinguished by thyrotoxicosis present in THypoKPP. FHypoKPP is caused by mutations in ionic channel genes calcium (CACN1AS), sodium (SCN4A) and potassium (KCNE3). Since both diseases are similar, we tested the hypothesis that THypoKPP could carry the same mutations described in FHypoKPP, being the paralysis a genetically conditioned complication of thyrotoxicosis. In 15 patients with THypoKPP, using target-exon PCR, CSGE screening, and direct sequencing, we excluded known mutations in CACN1AS and SCN4A genes. On the other hand, we were able to identify the R83H mutation in the KCNE3 gene in one sporadic case of THypoKPP, a man who had been asymptomatic until developing thyrotoxicosis caused by Graves’ disease; we confirmed the disease-causing mutation in 2 of 3 descendants. R83H was recently found in two FHypoKPP unrelated families, in which the mutant decreased outward potassium flux, resulting in a more positive resting membrane potential. We, therefore, identified the first genetic defect in THypoKPP, a mutation in the KCNE3 gene.

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