Figure 6.

Contribution of tetrodotoxin (TTX)-sensitive neuronal Na_vs to I_NaL in failing dog ventricular cardiomyocytes

A, raw current traces recorded in cultured cells in which SCN5A was silenced by the virally delivered Na_v1.5-siRNA before and after TTX (100 nm). B, difference current (Control-TTX), or neuronal I_NaL component along with the best single-exponent fit. Zero current represents difference between control recording and after TTX washout. Fit parameters and voltage-clamp protocol (same for A) is given in the panel. C, normalized I–V relationship of I_NaL before and after TTX recorded in freshly isolated cells. Current density was evaluated as an average within 200–220 ms after depolarization pulse for 2 s, V_h = −120 mV. Continuous lines are theoretical curves of steady-state activation. Note that TTX produced SSA shift to left (V_1/2 = −43 mV in control vs. –45 mV with TTX). Data are mean ± SEM.