What does this research mean for the field?

Expression of the CASQ2(D307H) mutation impairs sarcoplasmic reticulum calcium storing and release functions, destabilizing the calcium-induced calcium release mechanism and establishing the cellular basis for adrenergically mediated arrhythmias. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 13, 2004Circulation ResearchOpen Access

Abnormal Calcium Signaling and Sudden Cardiac Death Associated With Mutation of Calsequestrin

Q: What is the clinical evidence from this study?

Study design: Other. Population: Catecholaminergic polymorphic ventricular tachycardia. Intervention: Adenoviral-directed expression of CASQ2(D307H) vs. Adenoviruses expressing wild-type CASQ2 (CASQ2(WT)). Primary outcome: SR Ca2+ storing capacity and Ca2+ release functions.

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Key result

Expression of the CASQ2(D307H) mutation in rat myocytes impaired SR Ca2+ storing and release functions, destabilizing the Ca2+-induced Ca2+ release mechanism.

Population

Adult rat myocytes

Comparison

Adenoviral-directed expression of a canine CASQ2… vs Adenoviruses expressing wild-type CASQ2 (CASQ2)

Design

Preclinical

Authors

SVSerge Viatchenko‐KarpinskiUnited States Food and Drug Administration DTDmitry TerentyevNew Jersey Institute of Technology IGInna GyörkeAnna Needs Neuroblastoma Answers

Discussion

Member takes

Implication

Hypothesis-generating for CPVT mechanisms; leaves open translation to human therapies pending validation studies.

Structured PICO

Population

Adult rat myocytes

Intervention

Adenoviral-directed expression of a canine CASQ2 protein carrying the catecholaminergic polymorphic ventricular tachycardia-linked mutation D307H (CASQ2(D307H))

Comparator

Adenoviruses expressing wild-type CASQ2 (CASQ2(WT))

Outcome

Ca2+ storing capacity of the sarcoplasmic reticulum (SR) and Ca2+ signaling parameters (amplitude, duration, and rise time of Ca2+ transients and sparks)surrogate

The CASQ2(D307H) mutation impairs SR calcium handling and destabilizes calcium-induced calcium release, providing a cellular mechanism for adrenergically mediated arrhythmias in CPVT.

Cite This Study

Viatchenko‐Karpinski et al. (2004) studied Catecholaminergic polymorphic ventricular tachycardia. Adenoviral-directed expression of CASQ2(D307H) vs. Adenoviruses expressing wild-type CASQ2 (CASQ2(WT)) was evaluated on SR Ca2+ storing capacity and Ca2+ release functions. Expression of the CASQ2(D307H) mutation in rat myocytes impaired SR Ca2+ storing and release functions, destabilizing the Ca2+-induced Ca2+ release mechanism.

synapsesocial.com/papers/6a158b1dd64fa333899fcac7 https://doi.org/10.1161/01.res.0000115944.10681.eb

Topics

Ventricular arrhythmias

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Abnormal Calcium Signaling and Sudden Cardiac Death Associated With Mutation of Calsequestrin

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Topics

Abnormal Calcium Signaling and Sudden Cardiac Death Associated With Mutation of Calsequestrin

Discussion

Member takes

Implication

Structured PICO

Cite This Study

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Topics

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