Figure 4. Blockade of NO production prevents Cx43 hemichannel–mediated TA and arrhythmias in Dmd^mdx mice.

(A) Representative action potential traces of WT and Dmd^mdx isolated cardiomyocytes. Cells were stimulated with 1 μM Iso in the presence of 100 μM l-NAME. Arrow indicates electrical stimulation. (B) Quantification of TA induced by Iso observed in A. The number in parentheses indicates the n value. Comparisons between groups were made using 2-way ANOVA plus Tukey’s post hoc test; *P < 0.05. (C) Resting membrane potential of WT and Dmd^mdx cardiomyocytes. Comparisons between groups were made using 2-way ANOVA plus Tukey’s post hoc test. (D) Representative ECG traces of 5- to 6-month-old WT and Dmd^mdx mice that were previously treated or not with 2 mM l-NAME (an unspecific NOS blocker) via drinking water. ECG baseline and ECG after Iso treatment (5 mg/kg IP) are shown for comparison. (E) Arrhythmia score based on predetermined scale: 0, no arrhythmias; 1, single premature ventricular contractions (PVCs); 2, double PVCs; 3, triple PVCs or nonsustained ventricular tachycardia (VT); 4, sustained VT or atrioventricular (AV) block; and 5, death. *P < 0.0001 versus WT; ^†P < 0.0001 versus Dmd^mdx l-NAME. The number in parentheses indicates the n value. Statistical significance determined by 1-way ANOVA plus Tukey’s post hoc test.