Inducible over-expression of cardiac Nos1ap causes short QT syndrome in transgenic mice.

ABSTRACT: Recent evidence demonstrated that alterations in the QT interval duration on the ECG are not only determined by mutations in genes for ion channels, but also by modulators of ion channels. Changes in the QT interval duration beyond certain thresholds are pathological and can lead to sudden cardiac death. We here focus on the ion channel modulator nitric oxide synthase 1 adaptor protein (Nos1ap). Whole-cell patch-clamp measurements of a conditional transgenic mouse model exhibiting cardiac-specific Nos1ap over-expression revealed a Nos1ap-dependent increase of L-type calcium channel nitrosylation, which led to increased susceptibility to ventricular tachycardias associated with a decrease in QT duration and shortening of APD₉₀ duration. Survival was significantly reduced (60% aft

SUBMITTER: Jansch M 

PROVIDER: S-EPMC9808597 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature