May 24, 2007Circulation ResearchOpen Access

Dominant Negative Suppression of Rad Leads to QT Prolongation and Causes Ventricular Arrhythmias via Modulation of L-type Ca ²⁺ Channels in the Heart

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Why the study?

Does suppression of Rad activity via S105N mutation cause QT prolongation and ventricular arrhythmias in mice?

Structured PICO

Does suppression of Rad activity via S105N mutation cause QT prolongation and ventricular arrhythmias in mice?

Population

Guinea pig ventricular cardiomyocytes and a transgenic mouse model with cardiac-specific Rad suppression (overexpressing dominant negative mutant S105N Rad using the α-myosin heavy chain promoter)

Intervention

Overexpression of dominant negative mutant Rad (S105N)

Comparator

Wild-type littermate mice

Outcome

L-type Ca2+ current (ICa,L), action potential duration, QT interval, and occurrence of arrhythmiassurrogate

Suppression of Rad activity in the heart leads to QT prolongation and ventricular arrhythmias via upregulation of L-type Ca2+ channels, highlighting a novel arrhythmogenic signaling pathway.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Rad suppression merits exploration as arrhythmia modulator in mice; leaves open human relevance pending translational studies.

Cite This Study

Yada et al. (2007) studied this question.

synapsesocial.com/papers/6a72c1b33ce530166bc3601d https://doi.org/10.1161/circresaha.106.146399

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Dominant Negative Suppression of Rad Leads to QT Prolongation and Causes Ventricular Arrhythmias via Modulation of L-type Ca ²⁺ Channels in the Heart

Structured PICO

Discussion

Implication

Cite This Study

Dominant Negative Suppression of Rad Leads to QT Prolongation and Causes Ventricular Arrhythmias via Modulation of L-type Ca ²⁺ Channels in the Heart

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider