Key result
Dysgenic skeletal muscle in mice lacks the dihydropyridine receptor alpha 1 subunit, demonstrating its critical role as the voltage sensor for excitation-contraction coupling.
DHPR α1 absence causes E-C failure in mdg mice; leaves open translation to human myopathies.
Muscular dysgenesis (mdg) is a lethal autosomal, recessive mutation of mice. Skeletal muscle from dysgenic mice is paralyzed due to the failure of excitation-contraction (E-C) coupling. Considerable evidence indicates that this failure results from the absence of a specific gene product, the alpha 1 subunit of the skeletal muscle receptor for dihydropyridine calcium channel modifiers. This dihydropyridine receptor is hypothesized to function in E-C coupling of normal skeletal muscle as the voltage sensor that triggers calcium release from the sarcoplasmic reticulum and thereby causes contraction. The skeletal muscle dihydropyridine receptor is also postulated to function as the ion channel responsible for a slowly activating, dihydropyridine-sensitive calcium current (Islow). Dysgenic skeletal muscle lacks Islow but expresses, at low levels, a distinctly different dihydropyridine-sensitive calcium current (Idys). The channel protein underlying Idys is incapable of serving as a voltage sensor for E-C coupling. Studies using dysgenic skeletal muscle have provided significant insight into the role of dihydropyridine receptors in E-C coupling.
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Adams et al. (1990) conducted a review in Muscular dysgenesis. Muscular dysgenesis (mdg) mutation vs. Normal skeletal muscle was evaluated. Dysgenic skeletal muscle in mice lacks the dihydropyridine receptor alpha 1 subunit, demonstrating its critical role as the voltage sensor for excitation-contraction coupling.
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