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

In skeletal muscle, dihydropyridine (DHP) receptors control both Ca 2+ entry (L-type current) and internal Ca 2+ 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 Ca 2+ release and force production in muscle preparations of a mouse deficient in the γ1 subunit (γ–/–). The rate of internal Ca 2+ 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 Ca 2+ . 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 ( V 1/2 ) and voltage sensitivity ( k ) were not significantly different in γ–/– myotubes, either for internal Ca 2+ release activation or for the simultaneously measured L-type Ca 2+ conductance. The same was true for maximal Ca 2+ 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 Ca 2+ release and force production.