| Urea Transporters (UTs) are membrane proteins that mediate urea transporting through cell membrane, thus play an important role in the process of urinary concentrating mechanisms. The physiological functions of UT-B in renal were reported by several groups, however, the function of UT-1 out of renal were not further investigated. To investigate if UT-B knockout could modify the electrophysiology character of mice heart, we compared the difference of surface ECG, action potential and sodium current, potassium current, calcium current of ventricular myocytes between wild type mice and UT-B knockout mice, furthermore, we observed the effect of urea on surface ECG and sodium current, potassium current of ventricular myocytes in wild type mice. The results showed:1. UT-B gene knockout caused blockage type of arrhythmia in miceMice wereanesthetized by 20% Urethane and surface ECG (lead II) were recorded by BL-420E+ mutifunctional biosignal recording and analyzing system. In UT-B knockout group, arrhythmias were occurred in 45% mice (adult 30%, senior 60%), where as no arrhythmia was occurred in wild type C57 group. In the UT-B knock out group, 20% of senior mice occurred blockade types arrhythmias. Moreover, surface ECG also suggested that the P-R interval significantly prolonged in UT-B knock out mice and the QRS interval showed a higher variety.2. UT-B knockout induced changes in ventricular myocytes action potentioal parameters in mice.Action potentials were obtained using conventional intracellular recording technique and isolated heart perfusion technique. Compare to control group, the amplitude of action potential and Vmax were significantly decreased in the UT-B knock out group and action potential duration at 50% and 90% (APD50, APD90) was prolonged.3. UT-B knockout induced inhibition of sodium and potassium currents in ventricular myocytes of mice.Sodium current, potassium current,calcium current were measured in both wild type and UT-B knockout mice using whole cell patch clamp technique. Our result showed that, comparing to wild type mice, the sodium current and potassium current were signifacantly inhibited in UT-B knockout mice, whereas the calcium current did not show a significantly change.4. Intraperitoneal injection of urea induced blockage type of arrhythmia in wild type mice.After intraperitoneal injection of different concentrations of urea, heart rates were obviously decreased in 1-3 minutes, moreover, the blockage types of arrhythmia occurred in medium and high concentration groups in 3-15 minutes, grade II and grade III atrioventricular block were observed in high concentration group.5. Urea inhibited the sodium and potassium cutrrents in ventricular myocytes of wild type mice.After stable sodium current, potassium current were recorded in ventricular myocytes of wild type mice using patch clamp technique, different concentration of urea were applicated in extracellar solutions. The results suggested that urea significantly decreased the sodium current and potassium current, and the inhibition was dose-dependent.To the conclusion, our results are consistent with the predictions that there are some relationship between UT-B knockout and arrhythmia in mice. UT-B Knockout could change the electrophysiological characters in mouse myocytes, such as decreasing of APA and Vmax, prolonging of action potential duration, and sodium current and potassium current mechanism is involved in the change. The mechanism of the effects probably due to the UT-B knockout directly increases the blood urea concentration, thus high level of urea inhibits sodium current and potassium current of ventricular myocytes that decreases the excitability and conductibility of heart cells and results in blockage types of arrhythmias.
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