2,678 research outputs found
Mutations in the voltage-gated KV7.2 potassium channel associated with neonatal convulsions or myokymia
No full textNeonatal convulsions and peripheral nerve hyperexcitability are associated with mutations in the voltage-gated Kv7.2 (KCNQ2) potassium channel
No full textPeripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations
No full textBackground: Peripheral nerve hyperexcitability (PNH) is characterized by muscle overactivity due to spontaneous discharges of lower motor neurons usually associated with antibodies against voltage- gated potassium channels. PNH may also occur in combination with episodic ataxia or epilepsy caused by mutations in K(V)1.1 or K(V)7.2 channels. Only one PNH- associated mutation has been described so far in K(V)7.2 (R207W), in a family with both PNH and neonatal seizures. Methods: PNH was characterized by video and electromyography. The KCNQ2 gene was sequenced and K(V)7.2 channels were functionally characterized using two- microelectrode voltage-clamping in Xenopus oocytes. Results: In a patient with PNH without other neurologic symptoms, we identified a novel KCNQ2 mutation predicting loss of a charged residue within the voltage sensor of K(V)7.2 (R207Q). Functional analysis of both PNH-associated mutants revealed large depolarizing shifts of the conductance-voltage relationships and marked slowing of the activation time course compared to wild type (WT) channels, less pronounced for R207Q than R207W. Co-expression of both mutant with WT channels revealed a dominant negative effect reducing the relative current amplitudes after short depolarizations by > 70%. The anticonvulsant retigabine, an activator of neuronal K(V)7 channels, reversed the depolarizing shift. Conclusions: Mutations in KCNQ2 can cause idiopathic PNH alone and should be considered in sporadic cases. Both K(V)7.2 mutants produce PNH by changing voltage-dependent activation with a dominant negative effect on the WT channel. This distinguishes them from all hitherto examined Kv7.2 or K(V)7.3 mutations which cause neonatal seizures by haploinsufficiency. Retigabine may be beneficial in treating PNH
Mutations in the voltage-gated KV7.2 potassium channel associated with neonatal convulsions or myokymia
No full textNeonatal convulsions and peripheral nerve hyperexcitability are associated with mutations in the voltage-gated Kv7.2 (KCNQ2) potassium channel
No full textHypermetabolism in B–lymphocytes from malignant hyperthermia susceptible individuals
No full textMalignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B–lymphocytes, this study investigated whether cellular metabolism of native B–lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4–chloro–m–cresol (4-CmC) was used to challenge native B-lymphocytes in a real–time, metabolic assay based on a pH–sensitive silicon biosensor chip. At the cellular level, a dose–dependent, phasic acidification occurred with 4–CmC. The acidification rate, an indicator of metabolic activation, was significantly higher in B–lymphocytes from MHS patients and required 3 to 5 fold lower concentrations of 4–CmC to evoke similar acidification rates to MHN. Native B–lymphocytes from MHS individuals are more sensitive to 4–CmC than those from MHN, reflecting a greater Ca2+ turnover. The acidification response, however, was less pronounced than in muscle cells, presumably reflecting the lower expression of RyR1 in B–lymphocytes
Soğanlı Dere, Kirche A
No full textBeschriftung Hallensleben: „Soğanlı Dere / Kirche A = [Abstand gelassen] ? / [Bild] / Rott, S. 125, Abb. 36"http://difab.univie.ac.at (Digitales Forschungsarchiv Byzanz
Soğanlı, Karabaş Kilise
No full textBeschriftung Hallensleben:„Soğanlı Dere (südl. Ürgüp) / Karabaş Kilise / [Bild] / Rott S. 135, Abb. 41 / (vgl. Restle I, S. 106)"http://difab.univie.ac.at (Digitales Forschungsarchiv Byzanz
Soğanlı Dere, Kirche B
No full textBeschriftung Hallensleben: „SOĞANLI DERE – Gebiet / Höhlenkirche (B) GR / [Bild] / H. Rott: Kleinasiat. Denkmäler, 1908 / Abb. 37" [Siehe auch 012-400]http://difab.univie.ac.at (Digitales Forschungsarchiv Byzanz
Soğanlı Dere, Kirche A
No full textBeschriftung Hallensleben: „SOĞANLI DERE – Gebiet / Höhlenkirche (A) GR / [Bild] / H. Rott: Kleinasiat. Denkmäler, 1908 / Abb. 36"http://difab.univie.ac.at (Digitales Forschungsarchiv Byzanz
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