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Changes in ionic currents and reduced conduction velocity in hypertrophied ventricular myocardium of Xina-deficient mice [Anatol J Cardiol]
Anatol J Cardiol. 2007; 7(Suppl 1): 90-92

Changes in ionic currents and reduced conduction velocity in hypertrophied ventricular myocardium of Xina-deficient mice

Yu-Jun Lai1, Ya-Yu Chen2, Chio-Pei Cheng2, Jim Jung-Ching Lin3, Svetlana L. Chudorodova4, Irina M. Roshchevska4, Mikhail P Roshchevsky4, Yao-Chang Chen1, Cheng-I Lin2
1Institutes of Life Sciences & Physiology and Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan, R.O.C and 4Mackay Memorial Hospital, Taiwan, R.O.C.
2Institutes of Physiology National Defense Medical Center, Taipei, Taiwan, R.O.C
3Department of Biological Sciences, University of Iowa, Iowa City, Iowa, U.S.A.
4Komi Science Center, Ural Division, Russian Academy of Science, Syktyvkar, Russia

Objective: mXina, a downstream target gene of Nkx2.5 transcription factor, was shown to encode a proline-rich and Xin repeats-containing protein which localizes to the intercalated disc of adult hearts. Our previous voltage-clamp studies have shown that the ventricular myocytes of mXina-deficient mice exhibited a significant reduction in K+ currents (Ito and IK1), L-type Ca2+ currents, and maximum diastolic potential, leading to the development of early afterdepolarization (EAD) and arrhythmias. However, changes in cationic inward currents could also contribute to the genesis of EAD and arrhythmias in mXina-deficient mice. Methods: The present study aims to characterize changes in Na+ currents on depolarization and transient inward currents (Iti) on repolarization. Conduction velocity (CV) on the frontal surface of ventricles were also measured and compared. Results: Results of optical mapping on the Langendorff-perfused hearts at 37oC revealed a 36% reduction of CV in mXina-/- ventricle. Pacing (3 Hz)-induced tachyarrhythmias were more frequently found and ventricular fibrillation (VF, 21 Hz for 5 min) occurred in one out of 8 mXina-/- heart. When perfused at 30oC, no VF was observed in both types of preparations. Voltage-clamp study on isolated ventricular myocytes at 37oC shows increase in INa and Iti in mXina-/- cardiomyocytes thus could explain the occurrence of re-entrant triggered arrhythmias. Conclusion: The present results revealed that the CV was slower, but INa and Iti were increased in mXina-/-cardiomyocytes thus were prone to reentrant triggered arrhythmias. Hypothermia could reduce the occurrence of arrhythmias.

Keywords: Arrhythmia, conduction velocity, ionic currents, Xina-deficient murine heart, temperature, voltage-clamp studies


Yu-Jun Lai, Ya-Yu Chen, Chio-Pei Cheng, Jim Jung-Ching Lin, Svetlana L. Chudorodova, Irina M. Roshchevska, Mikhail P Roshchevsky, Yao-Chang Chen, Cheng-I Lin. Changes in ionic currents and reduced conduction velocity in hypertrophied ventricular myocardium of Xina-deficient mice. Anatol J Cardiol. 2007; 7(Suppl 1): 90-92


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