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.