Progressive muscle atrophy with hypokalemic periodic paralysis and calcium channel mutation

Meyer, Thomas; Jurkat‐Rott, Karin; Huebner, Angela; Lehmann‐Horn, Frank; Linke, P.; Landeghem, Frank K.H. van; Dullinger, Jörn S.; Spuler, Simone

doi:10.1002/mus.20825

Cited by 10 publications

(8 citation statements)

References 9 publications

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“…This mechanism may help to explain the permanent muscular atrophy and weakness observed in patients affected by hypoPP type -1 [15]. …”

Section: Discussionmentioning

confidence: 99%

“…Vacuole myopathy and t-tubule aggregates characterize muscle biopsies of hypoPP patients and K-depleted rats, a not genetic animal model of the disease [9,14]. Progressive muscular atrophy and permanent weakness were found in hypoPP patients carrying the CACNA1S gene mutations [15]. In Andersen’s Syndrome, the loss of function mutations of KCNJ2 gene encoding for the Kir2.1 is associated with arrhythmias, muscle weakness and skeletal muscle dysmorphisms as demonstrated in the Kir2.1 knockout mice, which exhibits a narrow maxilla and complete cleft of the secondary palate that may mimic the facial dysmorphology, observed in humans [9,16].…”

Section: Introductionmentioning

confidence: 99%

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Emerging Role of Calcium-Activated Potassium Channel in the Regulation of Cell Viability Following Potassium Ions Challenge in HEK293 Cells and Pharmacological Modulation

et al. 2013

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Emerging evidences suggest that Ca2+activated-K+-(BK) channel is involved in the regulation of cell viability. The changes of the cell viability observed under hyperkalemia (15 mEq/L) or hypokalemia (0.55 mEq/L) conditions were investigated in HEK293 cells expressing the hslo subunit (hslo-HEK293) in the presence or absence of BK channel modulators. The BK channel openers(10-11-10-3M) were: acetazolamide(ACTZ), Dichlorphenamide(DCP), methazolamide(MTZ), bendroflumethiazide(BFT), ethoxzolamide(ETX), hydrochlorthiazide(HCT), quercetin(QUERC), resveratrol(RESV) and NS1619; and the BK channel blockers(2x10-7M-5x10-3M) were: tetraethylammonium(TEA), iberiotoxin(IbTx) and charybdotoxin(ChTX). Experiments on cell viability and channel currents were performed using cell counting kit-8 and patch-clamp techniques, respectively. Hslo whole-cell current was potentiated by BK channel openers with different potency and efficacy in hslo-HEK293. The efficacy ranking of the openers at -60 mV(Vm) was BFT> ACTZ >DCP ≥RESV≥ ETX> NS1619> MTZ≥ QUERC; HCT was not effective. Cell viability after 24 h of incubation under hyperkalemia was enhanced by 82+6% and 33+7% in hslo-HEK293 cells and HEK293 cells, respectively. IbTx, ChTX and TEA enhanced cell viability in hslo-HEK293. BK openers prevented the enhancement of the cell viability induced by hyperkalemia or IbTx in hslo-HEK293 showing an efficacy which was comparable with that observed as BK openers. BK channel modulators failed to affect cell currents and viability under hyperkalemia conditions in the absence of hslo subunit. In contrast, under hypokalemia cell viability was reduced by -22+4% and -23+6% in hslo-HEK293 and HEK293 cells, respectively; the BK channel modulators failed to affect this parameter in these cells. In conclusion, BK channel regulates cell viability under hyperkalemia but not hypokalemia conditions. BFT and ACTZ were the most potent drugs either in activating the BK current and in preventing the cell proliferation induced by hyperkalemia. These findings may have relevance in disorders associated with abnormal K+ ion homeostasis including periodic paralysis and myotonia.

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“…This mechanism may help to explain the permanent muscular atrophy and weakness observed in patients affected by hypoPP type -1 [15]. …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emerging Role of Calcium-Activated Potassium Channel in the Regulation of Cell Viability Following Potassium Ions Challenge in HEK293 Cells and Pharmacological Modulation

et al. 2013

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“…Klinisch lassen sich Chloridkanal-und Natriumkanalmyotonien daran unterscheiden, dass bei ersterer die Augenlidmyotonie ein Warm-up zeigt, bei letzterer dagegen die Augenlidmyotonie paradox ist (28,43 Auch rasch progrediente Atrophien wurden beschrieben (31). Frauen mit inkompletter Penetranz für die Lähmungsepisoden können aber durchaus in späteren Lebensalter diese Myopathie aufweisen.…”

Section: Discussionunclassified

Hereditäre Muskelkanalopathien

Lehmann-Horn¹,

Jurkat-Rott²

2011

Nervenheilkunde

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ZusammenfassungElektrophysiologische und molekulargenetische Untersuchungen haben zur Erkenntnis geführt, dass bestimmte Muskelkrankheiten durch pathologisch veränderte Ionenkanäle verursacht sind. Diese Krankheiten werden deshalb Muskelkanalopathien genannt. Es sind dies die nicht dystrophischen Myotonien und die dyskaliämischen periodischen Paralysen, denen Störungen der Ionenkanäle des Plasmalemms zugrunde liegen, und CoreMyopathien und maligne Hyperthermie (MH), bei denen Kanäle der elektromechanischen Kopplung mutiert sind. Die Sichtweise, dass Muskelkanalopathien eher harmlose Erkrankungen sind, sollte revidiert werden. Nicht nur der Hypermetabolismus bei MH kann zu lebensbedrohlichen Krisen führen, sondern die periodischen Paralysen können ausgeprägte Dyskaliämien bewirken, welche die kardiale Erregungsausbreitung bedrohen. Die Hypokalämie ist bei der thyreotoxischen periodischen Paralysen am stärksten ausgeprägt. Abhängig von der zugrunde liegenden Mutation kommt es bei den periodischen Paralysen zu einer progressiven permanenten Muskelschwäche. Diese Schwäche kann mit einer Membrandepolarisation und einer konsekutiven intrazellulären Akkumulation von Natrium und Wasser erklärt werden. Substanzen, welche die Membran repolarisieren, können die Muskelkraft wiederherstellen und möglicherweise die Degeneration verhindern.

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“…However, progressive muscle atrophy represents a complex genetic disorder in which for most patients the genetic cause is unknown. In one such family, HypoPP has been linked to the known R528H variant in Ca V 1.1, suggesting the possibility that the CACNA1S gene may represent a genetic risk factor for progressive muscle atrophy [57].…”

Section: Hypokalemic Periodic Paralysis (Hypopp)mentioning

confidence: 99%

Skeletal muscle CaV1.1 channelopathies

Flucher

2020

Pflugers Arch - Eur J Physiol

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Ca V 1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known Ca V 1.1-related diseases are muscle diseases and the molecular and cellular disease mechanisms relate to the dual functions of Ca V 1.1 in this tissue. To date, four types of muscle diseases are known that can be linked to mutations in the CACNA1S gene or to splicing defects. These are hypo-and normokalemic periodic paralysis, malignant hyperthermia susceptibility, Ca V 1.1-related myopathies, and myotonic dystrophy type 1. In addition, the Ca V 1.1 function in EC coupling is perturbed in Native American myopathy, arising from mutations in the Ca V 1.1-associated protein STAC3. Here, we first address general considerations concerning the possible roles of Ca V 1.1 in disease and then discuss the state of the art regarding the pathophysiology of the Ca V 1.1-related skeletal muscle diseases with an emphasis on molecular disease mechanisms.

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Progressive muscle atrophy with hypokalemic periodic paralysis and calcium channel mutation

Cited by 10 publications

References 9 publications

Emerging Role of Calcium-Activated Potassium Channel in the Regulation of Cell Viability Following Potassium Ions Challenge in HEK293 Cells and Pharmacological Modulation

Emerging Role of Calcium-Activated Potassium Channel in the Regulation of Cell Viability Following Potassium Ions Challenge in HEK293 Cells and Pharmacological Modulation

Hereditäre Muskelkanalopathien

Skeletal muscle CaV1.1 channelopathies

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