Excitation-contraction coupling in skeletal muscle of a mouse lacking the dihydropyridine receptor subunit γ1


Corresponding author W. Melzer: University of Ulm, Department of Applied Physiology, Albert-Einstein-Allee 11, D-89069 Ulm, Germany. Email: werner.melzer@medizin.uni-ulm.de


  • In skeletal muscle, dihydropyridine (DHP) receptors control both Ca2+ entry (L-type current) and internal Ca2+ release in a voltage-dependent manner. Here we investigated the question of whether elimination of the skeletal muscle-specific DHP receptor subunit γ1 affects excitation-contraction (E–C) coupling. We studied intracellular Ca2+ release and force production in muscle preparations of a mouse deficient in the γ1 subunit (γ-/-).

  • The rate of internal Ca2+ release at large depolarization (+20 mV) was determined in voltage-clamped primary-cultured myotubes derived from satellite cells of adult mice by analysing fura-2 fluorescence signals and estimating the concentration of free and bound Ca2+. On average, γ-/- cells showed an increase in release of about one-third of the control value and no alterations in the time course.

  • Voltage of half-maximal activation (V1/2) and voltage sensitivity (k) were not significantly different in γ-/- myotubes, either for internal Ca2+ release activation or for the simultaneously measured L-type Ca2+ conductance. The same was true for maximal Ca2+ inward current and conductance.

  • Contractions evoked by electrical stimuli were recorded in isolated extensor digitorum longus (EDL; fast, glycolytic) and soleus (slow, oxidative) muscles under normal conditions and during fatigue induced by repetitive tetanic stimulation. Neither time course nor amplitudes of twitches and tetani nor force-frequency relations showed significant alterations in the γ1-deficient muscles.

  • In conclusion, the overall results show that the γ1 subunit is not essential for voltage-controlled Ca2+ release and force production.