Figure 4.

Reduction in oxidative/nitrosative stress as well as CaMKII and PKA inhibition ameliorates excessive intracellular Ca²⁺ responses to osmotic shock and hypersensitivity of EC-coupling in mdx myocytes isolated from 3- to 4-month-old mice (A and B) and reduces SR Ca²⁺ leak in cells from mature 12- 15-month-old mdx mice (C). In the experiments with osmotic shock (A), individual intracellular Ca²⁺ responses were determined as mean values of fluorescence recorded within the cell during 60 s after the shock, then averaged within each experimental group (e.g. each pharmacological intervention applied) and normalized to the averaged response under control conditions (no drug applied). In the EC-coupling gain experiments (B), averaged data within each experimental group were normalized to the values obtained in control (no drug applied) conditions. (C) Typical intracellular Ca²⁺ signals measured during the ‘leak’ protocol and averaged values of estimated SR Ca²⁺ leak under control conditions in WT and mdx cells and in mdx myocytes pretreated with various pharmacological agents (dashed bars). All values are listed in Supplementary material online, Table S1.