OBJECTIVE: To determine the characteristics of a TTX-sensitive Ca(2+) current that occurred only following remodelling after myocardial infarction in Wistar rat. METHODS: Using the whole-cell patch-clamp technique, we studied ionic inward current in myocytes isolated from four different ventricular regions of control Wistar rat hearts, or from hearts 4 to 6 months after ligation of the left coronary artery. Inward current characteristics were also analysed in Xenopus laevis oocytes that heterologously expressed the human sodium channel alpha-subunit Nav1.5. The effects of oxidative stress by hydrogen peroxide or tert-butyl-hydroxyperoxide as well as those of PKA-dependent phosphorylation, which partly mimic the pathological conditions, were investigated on control cardiomyocytes and Nav1.5-expressing oocytes. RESULTS: In Na-free solution, a low-threshold, tetrodotoxin-sensitive inward current was found in 20 out of 78 cells isolated from 16 post-myocardial infarcted (PMI) cardiomyocytes but not in cardiomyocytes from young and sham rat hearts. This current exhibited kinetics and pharmacological properties similar to the I(Ca(TTX)) current previously reported. I(Ca(TTX))-like current was critically dependent on extracellular Na(+) and was reduced by micromolar Na(+) concentrations. Neither in normal rat cardiomyocytes nor in Nav1.5-expressing oocytes could a I(Ca(TTX))-like current be elicited in Na(+)-free extracellular solution, even after oxidative stress or PKA-dependent phosphorylation. CONCLUSIONS: Our data suggest that I(Ca(TTX))-like current in PMI myocytes does not arise from classical Na(+) channels modified by oxidative stress or PKA phosphorylation and most probably represents a different Na(+) channel type re-expressed in some cells after remodelling.
OBJECTIVE: To determine the characteristics of a TTX-sensitive Ca(2+) current that occurred only following remodelling after myocardial infarction in Wistar rat. METHODS: Using the whole-cell patch-clamp technique, we studied ionic inward current in myocytes isolated from four different ventricular regions of control Wistar rat hearts, or from hearts 4 to 6 months after ligation of the left coronary artery. Inward current characteristics were also analysed in Xenopus laevis oocytes that heterologously expressed the human sodium channel alpha-subunit Nav1.5. The effects of oxidative stress by hydrogen peroxide or tert-butyl-hydroxyperoxide as well as those of PKA-dependent phosphorylation, which partly mimic the pathological conditions, were investigated on control cardiomyocytes and Nav1.5-expressing oocytes. RESULTS: In Na-free solution, a low-threshold, tetrodotoxin-sensitive inward current was found in 20 out of 78 cells isolated from 16 post-myocardial infarcted (PMI) cardiomyocytes but not in cardiomyocytes from young and sham rat hearts. This current exhibited kinetics and pharmacological properties similar to the I(Ca(TTX)) current previously reported. I(Ca(TTX))-like current was critically dependent on extracellular Na(+) and was reduced by micromolar Na(+) concentrations. Neither in normal rat cardiomyocytes nor in Nav1.5-expressing oocytes could a I(Ca(TTX))-like current be elicited in Na(+)-free extracellular solution, even after oxidative stress or PKA-dependent phosphorylation. CONCLUSIONS: Our data suggest that I(Ca(TTX))-like current in PMI myocytes does not arise from classical Na(+) channels modified by oxidative stress or PKA phosphorylation and most probably represents a different Na(+) channel type re-expressed in some cells after remodelling.
Authors: Bence Hegyi; László Bárándi; István Komáromi; Ferenc Papp; Balázs Horváth; János Magyar; Tamás Bányász; Zoltán Krasznai; Norbert Szentandrássy; Péter P Nánási Journal: Pflugers Arch Date: 2012-05-22 Impact factor: 3.657
Authors: Hui Sun; Diego Varela; Denis Chartier; Peter C Ruben; Stanley Nattel; Gerald W Zamponi; Normand Leblanc Journal: J Gen Physiol Date: 2008-07 Impact factor: 4.086
Authors: Bence Hegyi; István Komáromi; Kornél Kistamás; Ferenc Ruzsnavszky; Krisztina Váczi; Balázs Horváth; János Magyar; Tamás Bányász; Péter P Nánási; Norbert Szentandrássy Journal: Mar Drugs Date: 2013-06-14 Impact factor: 5.118