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L-type calcium current of rabbit cardiomyocytes in right ventricular outflow tract

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Objective The mechanism of idiopatic ventricular tachycardia, which mainly originates from right ventricular outflaw tract (RVOT), has not been completely understood. Previous research indicated that early after depolarisation (EAD) and delayed after depolarisation (DAD) more frequently occurred in RVOT cardiacmyocytes. The dispersion of action potential duration (APD) in RVOT cardiacmyocytes is wilder than that of RV cardiacmyocytes. The L-type calcium current, an important component of action potential (AP) plateau, has an apparent effect on APD. The aim of this study is to explore the electrophysiological characteristics of ICa-Lin RVOT cardiacmyocytesand the possible mechanism of idiopatic ventricular tachycardia arised from RVOT. Methods Rabbit cardiomyocytes in RVOT and in right ventricle (RV) were investigated with patch-clamp technique. Results RVOT cardiacmyocytes had a wider APD dispersion: the marked-prolonged APDs and the marked-shortened APDs both existed. 4-AP, an inhibitor of the transient outward potassium current (Ito), abolished the marked-shortened APDs. Some cardiomyoctes in rabbit RVOT showed significant prolongation in APD compared with RV (RVOT 727.25±44.52 ms; RV 481.0±97.12 ms; p.05). Some of their AP with long plateau could not even repolarise back to resting potential. In addition, EAD, AD and the second plateau response could emerge spontaneously in these cells. However, these phenomena were not observed in RV. These cells showed a higher current density of ICa-L compared with that of RV (RVOT 13.16±0.87 pA/pF; RV 8.59±1.97 pA/Pf; p0.05). Applying CdCl2, a blocker of ICa-L, could decrease the current density of ICa-L and diminish EAD, DAD and the second plateau response. Conclusion The wider APD dispersion of RVOT, the foundation of SQT and LQT in clinic, potentially played an important role in the genesis of right ventricular outflow tract ventricular tachycardia (RVOT-VT). Ito was a possible cause of markedly-abbreviated APD in RVOT cardiacmyocytes. Some cardiomyoctes in rabbit RVOT possessing a higher current density of ICa-L and showing marked prolongation in APD compared with RV, with the easier appearance of EAD and DAD concomitantly might be one of the mechanisms in RVOT-VT generation. This is the first study on the electrophysiological level to report the ICa-L current in rabbit RVOT cardiacmyocytes.
Title: L-type calcium current of rabbit cardiomyocytes in right ventricular outflow tract
Description:
Objective The mechanism of idiopatic ventricular tachycardia, which mainly originates from right ventricular outflaw tract (RVOT), has not been completely understood.
Previous research indicated that early after depolarisation (EAD) and delayed after depolarisation (DAD) more frequently occurred in RVOT cardiacmyocytes.
The dispersion of action potential duration (APD) in RVOT cardiacmyocytes is wilder than that of RV cardiacmyocytes.
The L-type calcium current, an important component of action potential (AP) plateau, has an apparent effect on APD.
The aim of this study is to explore the electrophysiological characteristics of ICa-Lin RVOT cardiacmyocytesand the possible mechanism of idiopatic ventricular tachycardia arised from RVOT.
Methods Rabbit cardiomyocytes in RVOT and in right ventricle (RV) were investigated with patch-clamp technique.
Results RVOT cardiacmyocytes had a wider APD dispersion: the marked-prolonged APDs and the marked-shortened APDs both existed.
4-AP, an inhibitor of the transient outward potassium current (Ito), abolished the marked-shortened APDs.
Some cardiomyoctes in rabbit RVOT showed significant prolongation in APD compared with RV (RVOT 727.
25±44.
52 ms; RV 481.
0±97.
12 ms; p.
05).
Some of their AP with long plateau could not even repolarise back to resting potential.
In addition, EAD, AD and the second plateau response could emerge spontaneously in these cells.
However, these phenomena were not observed in RV.
These cells showed a higher current density of ICa-L compared with that of RV (RVOT 13.
16±0.
87 pA/pF; RV 8.
59±1.
97 pA/Pf; p0.
05).
Applying CdCl2, a blocker of ICa-L, could decrease the current density of ICa-L and diminish EAD, DAD and the second plateau response.
Conclusion The wider APD dispersion of RVOT, the foundation of SQT and LQT in clinic, potentially played an important role in the genesis of right ventricular outflow tract ventricular tachycardia (RVOT-VT).
Ito was a possible cause of markedly-abbreviated APD in RVOT cardiacmyocytes.
Some cardiomyoctes in rabbit RVOT possessing a higher current density of ICa-L and showing marked prolongation in APD compared with RV, with the easier appearance of EAD and DAD concomitantly might be one of the mechanisms in RVOT-VT generation.
This is the first study on the electrophysiological level to report the ICa-L current in rabbit RVOT cardiacmyocytes.

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