Effects of local anaesthetics on the relationship between charge movements and contractile thresholds in frog skeletal muscle.

1. Charge movements to 10 mV steps at different potentials were studied in voltage-clamped frog skeletal muscle fibres in isotonic solutions that minimized ionic currents, under different pharmacological conditions. The earliest onset of detectable mechanical movement ('threshold') was assessed visually under magnification. 2. Charge movements in isotonic solutions were similar to those reported in hypertonic solutions, under identical pulse procedures. 3. In the absence of local anaesthetics, threshold occurred at a mean membrane potential of -55 mV, after the movement of 4.0 nC/muF of non-linear charge and when the membrane capacitance approximated values that corresponded to the onset of the 'Qgamma' charge movement component. 4. Lidocaine shifted the threshold in the hyperpolarizing direction to -62 mV, and reduced the amount of non-linear charge needed to reach threshold to 1.4 nC/muF. 5. The presence of tetracaine shifted threshold in the depolarizing direction to -39 mV, and more than doubled the amount of non-linear charge that had to move to reach threshold to 10.8 nC/muF. Much of this increase was attributed to the Qgamma component of charge movement. 6. It is concluded that more non-linear charge is required to initiate mechanical movement when calcium release by sarcoplasmic reticulum is inhibited by tetracaine, whereas less charge is so required when calcium re-uptake is being inhibited by lidocaine. Assuming earlier interpretations of the strength duration curve, this is consistent with charge movement preceding, rather than being a consequence of calcium release.