Occurrence of a tetrodotoxin-sensitive calcium current in rat ventricular myocytes after long-term myocardial infarction.
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.
INSERM U-390, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, F-34295 Montpellier Cedex 5, France.
Julio L
JL
Alvarez
Eduardo
E
Salinas-Stefanon
Gerardo
G
Orta
Tania
T
Ferrer
Karel
K
Talavera
Loipa
L
Galán
Guy
G
Vassort
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D009203:Myocardial Infarction / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology*; D020257:Ventricular Remodeling; D014982:Xenopus laevis
D015220:Calcium Channels; D015222:Sodium Channels; D014118:Toxins, Biological; D013779:Tetrodotoxin