Increased Activity of Calcium Leak Channels in Myotubes of Duchenne Human and mdx Mouse Origin

• Published in: Science (American Association for the Advancement of Science) Vol. 250; no. 4981; pp. 673 - 676
• Main Authors: Fong, Peying, Turner, Paul R., Denetclaw, Wilfred F., Steinhardt, Richard A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 02.11.1990; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium channels; Calcium Channels - drug effects; Calcium Channels - physiology; Cell membranes; Cells; Cellular biology; Diseases of striated muscles. Neuromuscular diseases; Duchenne muscular dystrophy; Dystrophin - genetics; Fluorescence; Genetics; Humans; Medical research; Medical sciences; Membrane potential; Membrane Potentials; Mice; Muscle fibers; Muscles - metabolism; Muscular dystrophies; Muscular Dystrophies - metabolism; Muscular dystrophy; Muscular Dystrophy, Animal - metabolism; Myoblasts; myotubules; Neurology; Nifedipine - pharmacology; Physiological aspects; Pipettes; Time constants; Human; Animal model; Nervous system diseases; Calcium; Rodentia; Electrophysiology; Ionic channel; Myotube; Genetic disease; Vertebrata; Striated muscle disease; Mammalia; Mouse; Duchenne muscular dystrophy
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2173137

Elevated free Ca$^{2+}$ concentrations found in adult dystrophic muscle fibers result in enhanced protein degradation. Since the difference in concentrations may reflect differences in entry, Ca$^{2+}$ leak channels in cultures of normal and Duchenne human myotubes, and normal and mdx murine myotubes, have been identified and characterized. The open probability of leak channels is markedly increased in dystrophic myotubes. Other channel properties, such as mean open times, single channel conductance, ion selectivity, and behavior in the presence of pharmacological agents, were similar among myotube types. Compared to the Ca$^{2+}$ concentrations in normal human and normal mouse myotubes, intracellular resting free Ca$^{2+}$ concentrations ([Ca$^{2+}$]$_i$) in myotubes of Duchenne and mdx origin were significantly higher at a time when dystrophin is first expressed in normal tissue. Taken together, these findings suggest that the increased open probability of Ca$^{2+}$ leak channels contributes to the elevated free intracellular Ca$^{2+}$ concentration in Duchenne human and mdx mouse myotubes.