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 ar...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 be- cause of the technical difficulties associated with examining this theory. The L-type calcium current （/Ca-L）, an important in- ward 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 character- istics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and Ic,-L were investigated us- ing 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 afterdepolariza- tion （EAD） and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a high- er current density for/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 ICa-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 Ica-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 ICa-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.展开更多
Background Atrial tachyarrhythmia (AT) is a common complication in patients who have undergone a Fontan operation. In this study, we investigated whether abnormal Ca2+ handling contributes to the Fontan operation-rela...Background Atrial tachyarrhythmia (AT) is a common complication in patients who have undergone a Fontan operation. In this study, we investigated whether abnormal Ca2+ handling contributes to the Fontan operation-related atrial arrhythmo-genic substrate. Methods Mongrel dogs were randomly assigned to sham and Fontan groups. The Fontan operation model was developed by performing an atriopulmonary anastomosis. After 14 days, an electrophysiological study was performed to evaluate the AT vulnerability. Ca2+ handling properties were measured by loading atrial cardiomyocytes (CMs) with fura-2 AM. The L-type Ca2+ (ICa?L) and Na+–Ca2+ exchanger (INCX) currents of the CMs were recorded by the whole-cell patch-clamp technique. The key Ca2+ handling proteins expression was assessed by Western blotting. Results The AT inducibility was higher in the Fontan group than in the sham group (85.71 vs. 14.29%, P < 0.05). The Fontan operation resulted in decreased Ca2+ transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca2+ content, but in enhanced diastolic intracellular Ca2+ concentration and SR Ca2+ leak in the atrial CMs. The spontaneous CaT events, triggered ectopic activity and INCX density were increased, but ICa?L density was reduced in CMs from the Fontan atria (all P<0.05). Additionally, the Fontan operation resulted in decreased SR Ca2+ ATPase expression and Cav1.2 expression, but in increased NCX1 and Ser2814-phosphorylated ryanodine receptor 2. The calmodulin-dependent protein kinase II expres-sion and function were markedly enhanced in the Fontan atria. Conclusion The Fontan operation caused atrial CM Ca2+ handling abnormalities that produced arrhythmogenic-triggered activity and increased vulnerability to AT in experimental Fontan dogs.展开更多
Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characte...Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characteristics j all the parameters of EAD showed cycle length-dependence; take-off potential of the first triggered burst played an important role in the generation of the other parameters ; hyper-polarization of the triggered brust enhanced the end of EAD; and the second plateau response might be used as an indicator of the capability of EAD generation of myocardiac cell. All those EADs were inhibited or abolished by nifedipine, tetrodotoxin or lidocaine. Potassium channel activators, lemakalim, thalium ion, acetyl-choline or high potassium could also inhibit or abolish the EADs. It is suggested that the EADs induced by different agents may base on a common mechanism ; all currents contributing to the plateau phase of the action potential play an important role in the generation of EAD.展开更多
Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological p...Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3- month （mo, young）, 9-mo （adult-l） and 12-too （adult-2） in wild-type （WT） and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential （APD50） showed prolongation in both 9-mo and 12-mo ones （9.2±0.9 ms of 9-mo and 10.3 ± 1.2 ms of 12- mo vs. 5.6± 0.3 ms of 3-mo）, while the 90 % repolarization of action potential （APD90） was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current （Ito） densities but increased L-type calcium current （ICa-L） densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age, It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice展开更多
文摘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 be- cause of the technical difficulties associated with examining this theory. The L-type calcium current （/Ca-L）, an important in- ward 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 character- istics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and Ic,-L were investigated us- ing 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 afterdepolariza- tion （EAD） and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a high- er current density for/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 ICa-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 Ica-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 ICa-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.
文摘Background Atrial tachyarrhythmia (AT) is a common complication in patients who have undergone a Fontan operation. In this study, we investigated whether abnormal Ca2+ handling contributes to the Fontan operation-related atrial arrhythmo-genic substrate. Methods Mongrel dogs were randomly assigned to sham and Fontan groups. The Fontan operation model was developed by performing an atriopulmonary anastomosis. After 14 days, an electrophysiological study was performed to evaluate the AT vulnerability. Ca2+ handling properties were measured by loading atrial cardiomyocytes (CMs) with fura-2 AM. The L-type Ca2+ (ICa?L) and Na+–Ca2+ exchanger (INCX) currents of the CMs were recorded by the whole-cell patch-clamp technique. The key Ca2+ handling proteins expression was assessed by Western blotting. Results The AT inducibility was higher in the Fontan group than in the sham group (85.71 vs. 14.29%, P < 0.05). The Fontan operation resulted in decreased Ca2+ transient (CaT) amplitude and sarcoplasmic reticulum (SR) Ca2+ content, but in enhanced diastolic intracellular Ca2+ concentration and SR Ca2+ leak in the atrial CMs. The spontaneous CaT events, triggered ectopic activity and INCX density were increased, but ICa?L density was reduced in CMs from the Fontan atria (all P<0.05). Additionally, the Fontan operation resulted in decreased SR Ca2+ ATPase expression and Cav1.2 expression, but in increased NCX1 and Ser2814-phosphorylated ryanodine receptor 2. The calmodulin-dependent protein kinase II expres-sion and function were markedly enhanced in the Fontan atria. Conclusion The Fontan operation caused atrial CM Ca2+ handling abnormalities that produced arrhythmogenic-triggered activity and increased vulnerability to AT in experimental Fontan dogs.
基金Project supported by the National Natural Science Foundation of China.
文摘Early afterdepolarization (EAD) in mouse atrial fibers was investigated under the treatment with aconitine, 3. 0 mmol/L K+ ,quinidine, ryanodine or Bay k 8644. All of these EADs possessed the following common characteristics j all the parameters of EAD showed cycle length-dependence; take-off potential of the first triggered burst played an important role in the generation of the other parameters ; hyper-polarization of the triggered brust enhanced the end of EAD; and the second plateau response might be used as an indicator of the capability of EAD generation of myocardiac cell. All those EADs were inhibited or abolished by nifedipine, tetrodotoxin or lidocaine. Potassium channel activators, lemakalim, thalium ion, acetyl-choline or high potassium could also inhibit or abolish the EADs. It is suggested that the EADs induced by different agents may base on a common mechanism ; all currents contributing to the plateau phase of the action potential play an important role in the generation of EAD.
文摘Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3- month （mo, young）, 9-mo （adult-l） and 12-too （adult-2） in wild-type （WT） and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential （APD50） showed prolongation in both 9-mo and 12-mo ones （9.2±0.9 ms of 9-mo and 10.3 ± 1.2 ms of 12- mo vs. 5.6± 0.3 ms of 3-mo）, while the 90 % repolarization of action potential （APD90） was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current （Ito） densities but increased L-type calcium current （ICa-L） densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age, It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice
