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

Abstract

The kinetics of mechanical activation of intact [Rana temporaria] fibers were examined with a voltage-clamp technique. Tetracaine (2 mM) increased 15- to 70-fold the time required to produce a just visible contraction by cell membrane depolarization. Displacement currents thought to be related to contractile activation remained in 2 mM tetracaine. Their characteristics were virtually identical to those found in the absence of the drug. Displacement currents also remained in fibers immobilized by treatment with 10 mM formaldehyde. Despite its effect on contraction of intact fibers, tetracaine did not diminish contraction tension when Ca was applied directly to the contractile proteins of skinned muscle fibers. The sensitivity of the myofilaments to Ca2+ also remained undiminished. When acting on intact fibers the drug must have inhibited Ca2+ released from the sarcoplasmic reticulum. It was estimated that 2 mM tetracaine diminished more than 10-fold the capacity for Ca2+-release in response to cell membrane depolarization. If muscle displacement currents represented events linking depolarization to Ca2+-release, then tetracaine must have been able to block the release without affecting the potential-sensing portion of the release regulating mechanism. Further experiments on skinned fibers have shown that tetracaine blocked or greatly diminished caffeine contractions, but that Cl-induced contractions of normal amplitude were still possible.