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

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Abstract
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.