Effects of tetracaine on displacement currents and contraction of frog skeletal muscle.

Abstract

The kinetics of mechanical activation of intact fibres were examined with a voltage-clamp technique. Tetracaine (2 mM) increases fifteen- to seventyfold the time required to produce a just visible contraction by cell membrane depolarization. 2. Displacement currents thought to be related to contractile activation remain in 2 mM tetracaine. Their characteristics are virtually identical to those found in the absence of the drug. Displacement currents also remain in fibres immobilized by treatment with 10 mM formaldehyde. 3. Despite its effect on contraction of intact fibres, tetracaine does not diminish contraction tension when Ca is applied directly to the contractile proteins of 'skinned' muscle fibres. The sensitivity of the myofilaments to Ca2+ also remains undiminished. 4. When acting on intact fibres the drug must therefore inhibit Ca2+-release from the sarcoplasmic reticulum. It is estimated that 2 mM tetracaine diminishes more than tenfold the capacity for Ca2+-release in response to cell membrane depolarization.5. If muscle displacement currents represent events linking depolarization to Ca2+-release, then tetracaine must be able to block the release without affecting the potential-sensing portion of the release regulating mechanism. 6. Further experiments on skinned fibres show that tetracaine blocks or greatly diminishes caffeine contractions, but that Cl-induced contractions of normal amplitude are still possible.