Figure 8. I_NaL alters myocardial function.

(a) Isometric contraction for young and old muscles. Scale bars, 500 ms, 0.5 mN mm⁻². Traces are superimposed in the inset. Scale bars, 50 ms, 0.5 mN mm⁻² (b) Properties of papillary muscles from male mice at 3–6 (Young, n=41) and 30–33 months (Old, n=24) are shown as mean±s.e.m. and scatter plots. *P<0.001 versus Young (Student's t-test); NP, non-parametric analysis. (c) Contraction for an old muscle prior (black traces) and following ranolazine exposure (Ran, red traces). Scale bars, 500 ms, 0.6 mN mm⁻². Traces are superimposed in the inset. Scale bars, 50 ms, 0.6 mN mm⁻². (d) Data for muscles of male mice at 3–5 (Young, n=11) and 30–33 months (Old, n=14) before and after exposure to 10 μM ranolazine are mean±s.e.m. and scatter plots. *P<0.001 versus KHB (Wilcoxon signed rank test); NP, non-parametric analysis. (e) Data for muscles of male mice at 3–6 months (n=9) before and after exposure to 1 mM 4-AP are mean±s.e.m. and scatter plots. *P≤0.001 versus KHB (paired t-test). (f) Data for muscles of mice at 3–9 months (n=9) before and after exposure to 10 nM ATX-II are mean±s.e.m. and scatter plots. *P<0.05 versus KHB (paired t-test). (g) Diastolic length–tension relations for twitching muscles stimulated at 6 Hz in the absence or presence of mexiletine (Mex). Muscles were obtained from male mice at 3 (Young, n=22; Young-Mex, n=6) and 30–33 months (Old, n=8; Old-Mex, n=8); data are mean±s.e.m. Fitting: second-order polynomial function (see Supplementary Table 3). *P<0.05 between selected fittings (one-way ANOVA with Bonferroni's post hoc test). (h) Diastolic length–tension relations of muscles from male mice at 3 months in the absence (Young, data as in g and presence of the I_NaL enhancer ATX-II (n=10); data are shown as mean±s.e.m. and fitted with a second order polynomial function. *P<0.0001 between fittings (Student's t-test). Parameters are reported in Supplementary Table 3.