Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Action potential duration is prolonged in many forms of heart disease, often as a result of reductions in Ca(2+)-independent transient outward K(+) currents (ie, I(to)). To examine the effects of a primary reduction in I(to) current in the heart, transgenic mice were generated that express a dominant-negative N-terminal fragment of the K(v)4.2 pore-forming potassium channel subunit under the control of the mouse alpha-myosin heavy chain promoter. Two of 6 founders died suddenly, and only 1 mouse successfully transmitted the transgene in mendelian fashion. Electrophysiological analysis at 2 to 4 weeks of age demonstrated that I(to) density was specifically reduced and action potential durations were prolonged in a subset of transgenic myocytes. The heterogeneous reduction in I(to) was accompanied by significant prolongation of monophasic action potentials. In vivo hemodynamic studies at this age revealed significant elevations in the mean arterial pressure, peak systolic ventricular pressures, and +/-dP/dt, indicative of enhanced contractility. Surprisingly, by 10 to 12 weeks of age, transgenic mice developed clinical and hemodynamic evidence of congestive heart failure. Failing transgenic hearts displayed molecular and cellular remodeling, with evidence of hypertrophy, chamber dilatation, and interstitial fibrosis, and individual myocytes showed sharp reductions in I(to) and I(K1) densities, action potential duration prolongation, and increased cell capacitance. Our results confirm that K(v)4.2 subunits contribute to I(to) in the mouse and demonstrate that manipulation of cardiac excitability may secondarily influence contractile performance.
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PMID:Targeted expression of a dominant-negative K(v)4.2 K(+) channel subunit in the mouse heart. 1190 10

The long QT syndrome (LQTS) is a cardiac disorder characterized by prolongation of the QT interval on electrocardiograms (ECGs), syncope and sudden death caused by a specific ventricular tachyarrhythmia known as torsade de pointes. LQTS is caused by mutations in ion channel genes including the cardiac sodium channel gene SCN5A, and potassium channel subunit genes KCNQ1, KCNH2, KCNE1, and KCNE2. Little information is available about LQTS mutations in the Chinese population. In this study, we characterized 42 Chinese LQTS families for mutations in the two most common LQTS genes, KCNQ1 and KCNH2. We report here the identification of four novel KCNQ1 mutations and three novel KCNH2 mutations. The KCNQ1 mutations include L191P in the S2-S3 cytoplasmic loop, F275S and S277L in the S5 transmembrane domain, and G306V in the channel pore. The KCNH2 mutations include L413P in transmembrane domain S1, E444D in the extracellular loop between S1 and S2, and L559H in domain S5. The location and character of these mutations expand the spectrum of KCNQ1 and KCNH2 mutations causing LQTS. Excitement, exercises, and stress appear to be the triggers for developing cardiac events (syncope, sudden death) for LQTS patients with KCNQ1 mutations F275S, S277L, and G306V, and all three KCNH2 mutations L413P, E444D and L559H. In contrast, cardiac events for an LQTS patient with KCNQ1 mutation L191P occurred during sleep or awakening from sleep. KCNH2 mutations L413P and L559H are associated with the bifid T waves on ECGs. Inderal or propanolol (a beta blocker) appears to be effective in preventing arrhythmias and syncope for an LQTS patient with the KCNQ1 L191P mutation.
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PMID:KCNQ1 and KCNH2 mutations associated with long QT syndrome in a Chinese population. 1244 76