A tetrodotoxin‐ and Mn 2+ ‐insensitive Na + current in Duchenne muscular dystrophy

Muscle myotube cultures were obtained from normal and Duchenne muscular dystrophy (DMD) biopsies by using an explant technique. The currentvoltage (I/V) curve of the whole sodium (Na + ) current (I Na ) in normal myotubes was similar to that obtained from DMD myotubes. However, the inactivation curve of the whole I Na was different in normal myotubes when compared to that obtained from DMD myotubes. Addition of 10 −4 tetrodotoxin (TTX, a fast I Na blocker) decreased the whole I Na in both preparations. The inorganic calcium (Ca 2+ ) blocker manganese (Mn 2+ ) completely blocked the remaining TTX‐resistant I Na of normal myotubes and decreased this current in DMD myotubes leaving behind a TTX‐ and Mn 2+ ‐insensitive I Na that was insensitive to the Ca 2+ blocker desmetoxyverapamil ((–)D888). The slow inward barium current (I Ba ) of both normal and DMD myotubes was blocked by Mn 2+ and (–)D888. However the kinetics of the slow channel in normal myotubes was different from that of DMD myotubes. This study demonstrates the presence of a TTX‐ and Mn 2+ ‐insensitive I Na in DMD myotubes. This channel may contribute to the increase of intracellular Na + ([Na] i ) in DMD and allow Ca 2+ to enter the cells through the Na + Ca 2+ exchanger, thus contributing to calcium loading.