Cells expressing the skeletal muscle Na+ channel SkM1 (which had an 18 mV depolarized shift in inactivation vs SCN5A) significantly increased conduction velocity in depolarized cardiac tissues.
Does expression of the skeletal muscle Na+ channel SkM1 improve cardiac excitability and conduction in depolarized tissues compared to the cardiac isoform SCN5A?
Gene and cell therapy using the skeletal muscle Na+ channel SkM1 improves cardiac excitability and conduction velocity in depolarized tissues more effectively than the cardiac isoform SCN5A.
The voltage-gated Na+ channel is a critical determinant of the action potential (AP) upstroke. Increasing Na+ conductance may speed AP propagation. In this study, we propose use of the skeletal muscle Na+ channel SkM1 as a more favorable gene than the cardiac isoform SCN5A to enhance conduction velocity in depolarized cardiac tissue. We used cells that electrically coupled with cardiac myocytes as a delivery platform to introduce the Na+ channels. Human embryonic kidney 293 cells were stably transfected with SkM1 or SCN5A. SkM1 had a more depolarized (18 mV shift) inactivation curve than SCN5A. We also found that SkM1 recovered faster from inactivation than SCN5A. When coupled with SkM1 expressing cells, cultured myocytes showed an increase in the dV/dtmax of the AP. Expression of SCN5A had no such effect. In an in vitro cardiac syncytium, coculture of neonatal cardiac myocytes with SkM1 expressing but not SCN5A expressing cells significantly increased the conduction velocity under both normal and depolarized conditions. In an in vitro reentry model induced by high-frequency stimulation, expression of SkM1 also enhanced angular velocity of the induced reentry. These results suggest that cells carrying a Na+ channel with a more depolarized inactivation curve can improve cardiac excitability and conduction in depolarized tissues.
Lü et al. (Fri,) conducted a other in Depolarized cardiac tissue. SkM1 expressing cells vs. SCN5A expressing cells was evaluated on Conduction velocity and dV/dtmax of the action potential. Cells expressing the skeletal muscle Na+ channel SkM1 (which had an 18 mV depolarized shift in inactivation vs SCN5A) significantly increased conduction velocity in depolarized cardiac tissues.
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