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

Shenghui Liang,Yuan Li,Taifeng Liu,Yan Wang,Yan Wang,Chenhui Lin

doi:10.1007/s11427-012-4265-3

Abstract

The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there are few studies investigating this because of the technical difficulties associated with examining this theory. The L-type calcium current (I (Ca-L)), an important inward current of the action potential (AP), plays an important role in arrhythmogenesis. The aim of this study was to explore differences in the APs of right ventricular (RV) and RVOT cardiomyocytes, and differences in electrophysiological characteristics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and I (Ca-L) were investigated using the patch-clamp technique. RVOT cardiomyocytes had a wider range of AP duration (APD) than RV cardiomyocytes, with some markedly prolonged APDs and markedly shortened APDs. The markedly shortened APDs in RVOT myocytes were abolished by treatment with 4-AP, an inhibitor of the transient outward potassium current, but the markedly prolonged APDs remained, with some myocytes with a long AP plateau not repolarizing to resting potential. In addition, early afterdepolarization (EAD) and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a higher current density for I (Ca-L) than RV myocytes (RVOT (13.16±0.87) pA pF(-1), RV (8.59±1.97) pA pF(-1); P<0.05). The I (Ca-L) and the prolonged APD were reduced, and the EAD and second plateau response disappeared, after treatment with nifedipine (10 μmol L(-1)), which blocks the I (Ca-L). In conclusion, there was a wider range of APDs in RVOT myocytes than in RV myocytes, which is one of the basic factors involved in arrhythmogenesis. The higher current density for I (Ca-L) is one of the factors causing prolongation of the APD in RVOT myocytes. The combination of EAD with prolonged APD may be one of the mechanisms of RVOT-VT generation.

Highlights

The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) is not clear
There were no significant differences between RVOT and RV myocytes when examined microscopically
Myocytes with AP duration (APD) which were shorter or longer than APDs of RV myocytes were studied as typical RVOT myocytes

Summary

Introduction

The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) is not clear. The higher current density for ICa-L is one of the factors causing prolongation of the APD in RVOT myocytes. Arrhythmogenesis, cardiomyocytes, ventricular tachycardia, right ventricular outflow tract, L-type calcium current, triggered activity, early afterdepolarization, patch-clamp technique. As IVT most commonly originates from the RVOT, it is important to study differences between the electrophysiological characteristics of RVOT and RV myocytes. Because of technical limitations, such as the difficulty in distinguishing morphologically between these myocyte types, there have been few experimental studies examining these differences, even though many clinical reports have speculated on the mechanisms underlying RVOT-VT [7,8]. This study examined the characteristics of the action potential (AP) and L-type calcium current (ICa-L) in RVOT and RV myocytes

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Conclusion