心衰中的分子医学系列（英文）-课件演示文稿.pptVIP

Na-Ch N1325S Ca-Ch SERCA Na/Ca exchanger VENTRICULAR MYOCYTE SR RyR2 TG-LQT3 cell Intracellular Sodium Overload in TG-LQT3 Cardiomyocytes 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 10 ms 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 NTG TG-WT TG-LQT3 + Caff 0.0 0.1 0.2 0.3 0.4 0.5 0.0 0.1 0.2 0.3 0.4 0.5 0 1 2 3 4 5 15 20 25 0 1 2 3 4 5 15 20 25 Transient Amplitude (FO/F) Time to 90% Recovery (T90r – ms) * * TG-LQT3 NTG TG-WT - Caff - Caff + Caff + Caff * Intracellular Calcium Abnormalities in TG-LQT3 Cardiomyocytes Sodium Channel Blocker TTX Attenuates Intracellular Calcium Abnormalities in TG-LQT3 Cardiomyocytes 0 Extracellular Calcium Attenuates Intracellular Calcium Abnormalities in TG-LQT3 Cardiomyocytes No NCX Current in TG-LQT3 Cardiomyocytes Conclusion Cardiomyocyte Apoptosis Progressive Loss of Cardiomyocytes Replacement of Myocardial Fibrosis Impaired Heart Structure (DCM) Defective Heart Function (HF) SCN5A N1325S mutation Intracellular Calcium Overload Late Sodium Current LQTS VT Sudden Death Intracellular Sodium Overload NCX ? This slide is just to confirm the genetic profile of the mouse models. On left hand side shows the construct that we used to generate our mice – the only difference here is the n1325s mutation. Top right-hand shows the southern blot for the copy number of the sodium channels while the lower right shows the western blot for the sodium channel protein expression levels. This means that we confirm the sodium channel expression is similar to our WT control. We did the southern blot and western blot to confirm the overexpression of the trangene. and try to identify any phyenotype from mutation or just sodium channel protein overexpression. Some of phenotype for this mouse model has been reported previously and the main characteristics are as follows: INa,L was easily detected in cardiomyocytes from TG-LQT3 mice, but not in cells from TG-WT or non-transgenic mice (NTG). Start in