CONCENTRATION-DEPENDENT EFFECTS OF TETRACAINE ON EXCITATION-CONTRACTION COUPLING IN FROG SKELETAL-MUSCLE FIBERS

The effects of low (10-100 mu M) concentrations of tetracaine on intra membrane charge movement and on the rate of calcium release (R(rel)) f rom the sarcoplasmic reticulum (SR) were studied in cut skeletal muscl e fibres of the frog using the voltage clamp technique. The fibres wer e mounted in a single or double vaseline gap chamber to study the even ts near the contraction threshold or in a wide membrane potential rang e. Although the 'hump' component of charge movement (Q(gamma)) was sup pressed to some extent, the voltage dependence and the parameters of t he Boltzmann distribution were not modified significantly at tetracain e concentrations below 50 mu M. At 50 and 100 mu M of tetracaine the m idpoint voltage of the Boltzmann distribution was shifted to higher me mbrane potentials and the steepness was decreased. The total available charge remained the same at all concentrations tested. Using fura-2 t o measure calcium transients at 100 mu M tetracaine the threshold for calcium release was found to be significantly shifted to more positive membrane potentials. Tetracaine reversibly suppressed both the early inactivating peak and the steady-level of R(rel) but the concentration dependence of these effects was markedly different. The inactivating component of calcium release was decreased with a Hill coefficient of approximately 1 and half effective concentration of 11.8 mu M while th e steady-level was decreased with a Hill coefficient of greater than 2 and a half effective concentration of 47.0 mu M. These results favour two sites of action where tetracaine would suppress the calcium relea se from the SR.