The skeletal muscle L-type calcium channel or dihydropyridine receptor (DHPR) plays an integral role in excitation-contraction (E-C) coupling. Its activation initiates three sequential events: charge movement (Q_r), calcium release, and calcium current (I_Ca,L). This relationship suggests that changes in Q_r might affect release and I_Ca,L. Here we studied the effect of gabapentin (GBP) on the three events generated by DHPRs in skeletal myotubes in culture. GBP specifically binds to the ₂/₁ subunit of the brain and skeletal muscle DHPR. Myotubes were stimulated with a protocol that included a depolarizing prepulse to inactivate voltage-dependent proteins other than DHPRs. Gabapentin (50 µM) significantly increased Q_r while decreasing the rate of rise of calcium transients. Gabapentin also reduced the maximum amplitude of the I_Ca,L (as we previously reported) without modifying the kinetics of activation. Exposure of GBP-treated myotubes to 10 µM nifedipine prevented the increase of Q_r promoted by this drug, indicating that the extra charge recorded originated from DHPRs. Our data suggest that GBP dissociates the functions of the DHPR from the initial voltage-sensing step and implicates a role for the ₂/₁ subunit in E-C coupling.