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Tetracaine can inhibit contractions initiated by a voltage‐sensitive release mechanism in guinea‐pig ventricular myocytes
Author(s) -
Mason Cindy A.,
Ferrier Gregory R.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0851n.x
Subject(s) - tetracaine , contraction (grammar) , chemistry , voltage clamp , ryanodine receptor , biophysics , muscle contraction , current clamp , patch clamp , myocyte , membrane potential , intracellular , medicine , anesthesia , biochemistry , biology , receptor , lidocaine
1 Effects of tetracaine on membrane currents and cell shortening were measured with high resistance electrodes, single‐electrode voltage clamp (switch clamp) and a video edge detector at 37 °C in cardiac ventricular myocytes. 2 Sequential voltage steps from ‐65 mV to ‐40 and 0 mV were used to activate two mechanisms of excitation‐contraction (EC) coupling separately. The step to ‐40 mV activated the voltage‐sensitive release mechanism (VSRM); the step to 0 mV1 activated Ca 2+ ‐induced Ca 2+ release (CICR) coupled to inward Ca 2+ current ( I L ). 3 Exposure to 100‐300 μ m tetracaine inhibited VSRM contractions but not CICR contractions. Inhibition of VSRM contractions was independent of I Na blockade. In contrast, 100 μ m Cd 2+ blocked I L and CICR contractions, but not VSRM contractions. Simultaneous application of both agents blocked both mechanisms of EC coupling. 4 Contraction‐voltage relationships were sigmoidal when the VSRM was available. However, when the VSRM was inhibited with 100‐300 μ m tetracaine, contraction‐voltage relationships became bell‐shaped. The tetracaine‐insensitive contractions were abolished by 0.1 μ m ryanodine, indicating that they were dependent on release of SR Ca 2+ . 5 At a higher concentration (1 mM) tetracaine also inhibited I L and contractions triggered by I L ; however, the time course of effects on I L and associated contractions were different than for VSRM contractions. 6 With continuous application of tetracaine, the VSRM remained inhibited although SR Ca 2+ stores increased 4‐fold as assessed with caffeine. CICR contractions were not inhibited and maximum amplitude of contraction was not reduced. 7 Rapid application of tetracaine just before and during test steps also inhibited VSRM contractions, but without significantly affecting sarcoplasmic reticulum (SR) Ca 2+ stores or CICR contractions. Maximum amplitude of contraction was reduced. 8 Rapid application of tetracaine (100‐300 μ m ) allows preferential inhibition of the VSRM and provides a pharmacological method to assess the contribution of the VSRM to EC coupling.