Figure 3.

Use-dependent block of I_Na by ranolazine (RAN, 30 μM). A: Mean normalized current amplitudes recorded by a series of 40 pulses to −30 mV at diastolic interval (DI) of 110 ms (circles), 60 ms (squares), and 40 ms (triangles) in atrial myocytes (filled symbols) from holding potentials (HPs) of (i) −120 mV (n = 6), (ii) −110 mV (n = 6), and (iii) −100 mV (n = 5) in the presence of RAN. Currents were normalized to the currents elicited in the absence of RAN by the corresponding pulse number. B: Mean normalized current amplitudes recorded using the same protocol as used in A from ventricular myocytes (open symbols) in the presence of RAN from HPs of (i) −120 mV (n = 5), (ii) −110 mV (n = 6), and (iii) −100 mV (n = 9). C: The mean percentage total block elicited by the 40th pulse at DIs of 110, 60, and 40 ms from atrial (filled columns) and ventricular (open columns) myocytes at HPs of (i) −120 mV, (ii) −110 mV, and (iii) −100 mV (sample sizes correspond to A and B). Total block was significantly different by factorial mixed analysis of variance (P < .001). Data were significantly different by DI (P < .001), HP (P < .001), and cell type (P < .001). There was a significant interaction between cell type and HP (P = .02). In Bonferroni post hoc tests, the effect of 110 ms DI was significantly different from 60 ms (P = .014) and 40 ms (P < .001) but there was no statistical confidence in the difference between DI of 60 ms and 40 ms (P = .558). Similarly, the effect of an HP of −120 mV was significantly different from both −110 mV (P < .001) and −100 mV (P < .001) and the effect of −110 mV was significantly different from −100 mV (P = .046).