Figure 3.

Voltage-gated Na⁺ currents in arteries and effect of ranolazine. Effect of the addition of cumulative doses of KCl (1 to 40 mM) on a Na_v channel-dependent component of contraction recorded in the absence (left) and the presence of ranolazine (20 μM) (right) in rat aortic rings. Graphs summarize the dose-response curves obtained for KCl. Averaged data expressed as percentage of the maximal contraction induced by KCl (n = 15) (A). Reproduced from Figure 3B in [142]. (B) Typical Na⁺ current with an I_Na,late evoked at a test potential of 0 mV from a holding potential of −100 mV, using the whole-cell patch-clamp technique, in a primary cultured human coronary myocyte (HCM) (unpublished personal data). The experiment was performed as described [161]. (C) Increasing effect of the Na⁺ channel agonist veratridine (Vt; 10 μM) on intracellular Ca²⁺ ([Ca²⁺]_i) in a fura-2–loaded HCM (unpublished personal data). The experiment was performed as described in [162]. (D) Antagonist effect of ranolazine (20 µM) on a veratridine-induced I_Na in a primary cultured rat aortic myocyte. The I_Na current was evoked by a 40 ms ramp from −80 mV to +40 mV, following a 2-sec prepulse at −100 mV, from a holding potential of −80 mV in the presence of Vt (100 μM). Tetrodotoxin (TTX; 1 µM) was added after ranolazine to block all I_Na current. Arrows indicate the current’s activation and maximal amplitude with the corresponding voltages. Reproduced from Figure 1A in [142].