Dantrolene-Induced Inhibition of Skeletal L-Type Ca²⁺ Current Requires RyR1 Expression

Figure 1

Dantrolene does not affect the 𝐼-𝑉 relationship in of the fast skeletal muscle Na⁺ current. Representative recordings of skeletal 𝐼_Na elicited by 20 ms depolarizations from the steady holding potential of −80 mV to the indicated test potentials (illustrated at top) are shown for untreated control myotubes (a) and myotubes exposed to 10 𝜇M Dantrolene (b). (c) Comparison of peak 𝐼-𝑉 relationships for control (⚫; 𝑛=20) and Dantrolene-treated (⚪; 𝑛=11) myotubes. Currents were evoked at 0.1 Hz by test potentials ranging from −70 mV through +40 mV in 10 mV increments. Peak current amplitudes were normalized by linear cell capacitance (pA/pF). Smooth 𝐼-𝑉 curves were fit by (1) (see “Section 2”) with the following respective parameters for control and Dantrolene-treated groups: 𝐺_max=305±43 and 355±44 nS/nF; 𝑉_1/2=−9.8±1.7 and −7.4±1.3 mV; 𝑘=6.9±0.3 and 7.2±0.2 mV. (d) comparison of conductance-voltage relationships for control and Dantrolene-treated myotubes. The average normalized conductance values (derived from 𝐼-𝑉 data using (2); see Section 2) were fit by (3) with the following respective parameters for control and Dantrolene-treated groups: 𝑉_1/2=−9.9±1.8 and −5.9±3.0 mV; 𝑘=6.9±0.3 and 7.9±1.0 mV. Throughout, data are given as mean±SEM, with the numbers in parentheses indicating the number of myotubes tested. For all the data given, the calculated average voltage error was <5 mV.