Figure 9. Effect of the RyR1 inhibitor dantrolene on charge movement.

A, exposure of control fibres to 40 μm dantrolene for 3 min suppressed the action potential evoked Ca²⁺ transient by about 35%, measured with high speed confocal microscopy and Fluo4-AM Ca²⁺ indicator dye. This reduction in the Ca²⁺ transient recapitulates the suppression seen in KO fibres (Prosser et al. 2007). The inset shows the normalized peak values of the Ca²⁺ transient (reported as ΔF/F₀±s.e.m.) as a function of time of exposure to dantrolene. B, charge movement currents from a control fibre (left), before (blue trace) and after (brown trace) 3 min exposure to 40 μm dantrolene in the bath, and the resulting difference current (orange trace). As can be seen, the RyR inhibitor dantrolene suppressed a temporally delayed hump component at intermediate voltages, without affecting the initial component of charge movement currents, similar to the difference current between WT and KO fibres. On the right of the figure are charge movement currents elicited by the same voltage steps in 4 KO fibres exposed to the same concentration of dantrolene (red traces). There was no suppression of charge movement in any of these fibres. C, Q–V relationship of 6 control fibres before and after treatment with dantrolene. The steeply voltage-dependent difference component (Ctrl – Dantro; orange Q–V) was fitted to a single Boltzmann function to −10 mV and displayed parameters Q_max= 6.3 nC μF⁻¹, V_half=−21.5 mV and k= 3.0 mV. At higher voltages the difference component decreased monotonically with voltage and was therefore fitted to a linear function.