L-type Calcium Current In Right Ventricular Outflow Tract Myocytes Of Rabbit Heart

ObjectiveThe mechanism of idiopathic ventricular tachycardia originating fromthe right ventricular outflow tract (RVOT) is not clear. Many clinicalreports have suggested a mechanism of triggered activity. However, thereare few studies investigating this because of the technical difficultiesassociated with examining this theory. The L-type calcium current (ICa-L),an important inward current of the action potential (AP), plays animportant role in arrhythmogenesis. The aim of this study was to exploredifferences in the APs of right ventricular (RV) and RVOT cardiomyocytes,and differences in electrophysiological characteristics of the ICa-Linthese myocytes.MethodsRabbit RVOT and RV myocytes were isolated and their AP and ICa-Lwereinvestigated using the patch-clamp technique.ResultsRVOT cardiomyocytes had a wider range of AP duration (APD) than RVcardiomyocytes, with some markedly prolonged APDs and markedly shortenedAPDs. The markedly shortened APDs in RVOT myocytes were abolished bytreatment with4-AP, an inhibitor of the transient outward potassiumcurrent, but the markedly prolonged APDs remained, with some myocyteswith 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 highercurrent density for ICa-Lthan RV myocytes (RVOT13.16±0.87pA pF-1, RV8.59±1.97pA pF-1; P<0.05). The ICa-Land the prolonged APD were reduced,and the EAD and second plateau response disappeared, after treatment withnifedipine (10μmol L-1), which blocks the ICa-L.Conclusions1. There was a wider range of APDs in RVOT myocytes than in RV myocytes,which is one of the basic factors involved in arrhythmogenesis.2. The higher current density for ICa-Lis one of the factors causingprolongation of the APD in RVOT myocytes.3. The combination of EAD with prolonged APD may be one of the mechanismsof RVOT-VT generation.