Right ventricular preload and afterload challenge induces contractile dysfunction and arrhythmia in isolated hearts of dystrophin-deficient male mice.

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy due to mutations in the dystrophin gene. Diaphragmatic weakness in DMD causes hypoventilation and elevated afterload on the right ventricle (RV). Thus, RV dysfunction in DMD develops early in disease progression.

Ca-saturated calmodulin binds tightly to the N-terminal domain of A-type fibroblast growth factor homologous factors.

Voltage-gated sodium channels (Nas) are tightly regulated by multiple conserved auxiliary proteins, including the four fibroblast growth factor homologous factors (FGFs), which bind the Na EF-hand like domain (EFL), and calmodulin (CaM), a multifunctional messenger protein that binds the Na IQ motif. The EFL domain and IQ motif are contiguous regions of Na cytosolic C-terminal domains (CTD), placing CaM and FGF in close proximity. However, whether the FGFs and CaM act independently, directly associate, or operate through allosteric interactions to regulate channel function is unknown.