Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inward rectifier potassium current in the heart, I(K1), has been suggested to play a significant role in cardiac excitability by contributing to the late phase of action potential (AP) repolarization and the stabilization of resting potential. To further assess the role of I(K1) in cardiac excitability we have produced transgenic mice expressing a dominant-negative subunit of the Kir2.1 channel, a major molecular determinant of I(K1) in the heart, and studied the effects of I(K1) suppression on major potassium currents, APs and the overall electrical activity of the heart. Kir2.1 channel subunits with a mutated signature sequence (AAA for GYG substitution) were expressed in the heart under control of the alpha-myosin heavy chain promoter. Two lines of transgenic mice were established, both expressing high levels of Kir2.1-AAA-GFP (GFP, green fluorescent protein) subunits in all major parts of the heart. In ventricular myocytes isolated from transgenic mice, I(K1) was reduced by 95% in both lines, leading to a significant prolongation of APs. Surface ECG recordings from anesthetized transgenic mice revealed significant changes in key parameters of excitability, including prolongation of QRS complexes and QT intervals. This study confirms the significant role of I(K1) in control of AP repolarization and major ECG intervals in the intact heart.
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PMID:Dominant-negative suppression of I(K1) in the mouse heart leads to altered cardiac excitability. 1268 16

Cardiac ATP-sensitive K+ (K(ATP)) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression with the alpha-myosin heavy chain promoter. Weight gain and development after birth of these mice were similar to nontransgenic mice, but an increased mortality was noted after the age of 4-5 mo. Transgenic mice lacked cardiac K(ATP) channel activity as assessed with patch clamp techniques. Consistent with a decreased current density observed at positive voltages, the action potential duration was increased in these mice. Some myocytes developed EADs after isoproterenol treatment. Hemodynamic measurements revealed no significant effects on ventricular function (apart from a slightly elevated heart rate), whereas in vivo electrophysiological recordings revealed a prolonged ventricular effective refractory period in transgenic mice. The transgenic mice tolerated stress less well as evident from treadmill stress tests. The proarrhythmogenic features and lack of adaptation to a stress response in transgenic mice suggest that these features are intrinsic to the myocardium and that K(ATP) channels in the myocardium have an important role in protecting the heart from lethal arrhythmias and adaptation to stress situations.
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PMID:Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits. 1650 Oct 27