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A tetrodotoxin‐ and Mn 2+ ‐insensitive Na + current in Duchenne muscular dystrophy
Author(s) -
Bkaily Ghassan,
Jasmin Gaétan,
Tautu Constantin,
Prochek Libuse,
Yamamoto Tatsuo,
Sculptoreanu Adrian,
Peyrow Mehrzad,
Jacques Danielle
Publication year - 1990
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880131009
Subject(s) - myogenesis , duchenne muscular dystrophy , tetrodotoxin , chemistry , sodium channel , myocyte , sodium , calcium , biophysics , medicine , endocrinology , biology , organic chemistry
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.