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The effect of tetracaine on stimulated contractions, sarcoplasmic reticulum Ca 2+ content and membrane current in isolated rat ventricular myocytes
Author(s) -
Overend C. L.,
O'Neill S. C.,
Eisner D. A.
Publication year - 1998
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.1469-7793.1998.759bs.x
Subject(s) - tetracaine , chemistry , endoplasmic reticulum , contraction (grammar) , sarcolemma , calcium , biophysics , voltage clamp , myocyte , medicine , membrane potential , membrane , anesthesia , biochemistry , biology , organic chemistry , lidocaine
1 The effects of tetracaine were examined on rat ventricular myocytes. In both field‐stimulated and voltage‐clamped cells tetracaine (100–200 μM) produced an initial decrease of contraction before a recovery towards the control level. Removal of tetracaine produced a transient overshoot of contraction to levels greater than the control. 2 The transient decrease of contraction produced by tetracaine was accompanied by a small transient increase in the integral of the L‐type Ca 2+ current and a larger transient decrease of the Na + ‐Ca 2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca 2+ . On removal of tetracaine there was an increase of the Na + ‐Ca 2+ exchange current. Before the addition of tetracaine, calculated Ca 2+ influx and efflux across the sarcolemma were approximately equal. On adding tetracaine, efflux was transiently less than influx and, on removal of tetracaine, efflux was greater than influx. 3 These changes in Ca 2+ fluxes result in an increase of cell Ca 2+ during exposure to tetracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca 2+ and integrating the resulting Na + ‐Ca 2+ exchange current. 4 It is concluded that the effects of tetracaine can be accounted for by depression of calcium‐induced Ca 2+ release (CICR). The response is transient because the inhibition is compensated for by an increase of SR Ca 2+ content such that there is no steady‐state effect on the magnitude of the systolic Ca 2+ transient. The consequences of this result for the effects of other modulators of CICR are discussed.