Rate-dependent QT shortening mechanism for the LQT3 ΔKPQ mutant
نویسندگان
چکیده
منابع مشابه
Intrinsic mechanism of the enhanced rate-dependent QT shortening in the R1623Q mutant of the LQT3 syndrome.
OBJECTIVE In the type 3 long QT syndrome (LQT3), arrhythmia events tend to occur at rest or during sleep. One of the mutations, R1623Q, is located in the voltage sensor of the cardiac sodium channel (hH1), and patients with R1623Q mutation have been also reported to show bradycardia-dependent cardiac events. Although the mutant channel has been characterized by inactivation gating defects, the ...
متن کاملLight phase-restricted feeding slows basal heart rate to exaggerate the type-3 long QT syndrome phenotype in mice.
Long QT syndrome type 3 (LQT3) is caused by mutations in the SCN5A-encoded Nav1.5 channel. LQT3 patients exhibit time of day-associated abnormal increases in their heart rate-corrected QT (QTc) intervals and risk for life-threatening episodes. This study determines the effects of uncoupling environmental time cues that entrain circadian rhythms (time of light and time of feeding) on heart rate ...
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Mutations of the SCN5A gene can significantly alter the function of cardiac myocyte sodium channels leading to increased risk of ventricular arrhythmia. Over the past decade, detailed Markov models of the action potential of cardiac cells have been developed. In such models, the effects of a drug can be treated as alterations in on- and off rates between open and inactivated states on one hand,...
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BACKGROUND The cardiac sodium channel (SCN5A) mutation L1825P has been identified in a patient with drug-induced torsade de pointes precipitated by the IKr blocker cisapride. Although L1825P generates late sodium current typical of SCN5A-linked long-QT syndrome (LQT3) in vitro, the patient reported had a normal QT interval before administration of the drug. To address this discrepancy, we teste...
متن کاملPurkinje Cells as Sources of Arrhythmias in Long QT Syndrome Type 3
Long QT syndrome (LQTS) is characterized by ventricular arrhythmias and sudden cardiac death. Purkinje cells (PC) within the specialized cardiac conduction system have unique electrophysiological properties that we hypothesize may produce the primary sources of arrhythmia in heritable LQTS. LQTS type 3 (LQT3) transgenic mice harboring the ΔKPQ(+/-) mutation were crossed with Contactin2-EGFP BAC...
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ژورنال
عنوان ژورنال: Cardiovascular Research
سال: 2002
ISSN: 0008-6363
DOI: 10.1016/s0008-6363(02)00265-1