Fig. 5.

Sodium channel blockade and antimyotonic effect of propranolol enantiomers. (A) The racemic DL-propranolol and single propranolol S(−) and R(+) enantiomers (100 μmol/l) were tested on sodium currents measured in HEK293 cells permanently transfected with the human skeletal muscle hNav1.4 isoform of sodium channels. Sodium currents were elicited by depolarizing the cells for 20 ms at −30 mV from a holding potential of −120 mV every 10 or 0.1 s (i.e. 0.1 Hz or 10 Hz stimulation frequency, respectively). Sodium current traces recorded in a representative cell are shown in control condition (CTRL) and after acute application of R-propranolol at 0.1 and 10 Hz stimulation frequency. (B) Percentage of sodium current block by DL-propranolol and single propranolol enantiomers (100 μmol/l) at 0.1 or 10 Hz stimulation frequency. Each bar is the mean ± S.E.M. from at least 3 cells. (C) In vivo antimyotonic effect in 9-AC treated rats of DL-propranolol and single propranolol enantiomers (15 mg/kg) expressed as the percentage of TRR reduction with respect to rats receiving drug vehicle alone. Each bar is the mean ± S.E.M. from at least 3 animals. No significant difference in sodium channel blockade and in vivo antimyotonic effects was found between the two single enantiomers and racemic propranolol (P > 0.05 with one-way ANOVA).