THE EFFECT OF TETRACAINE ON STIMULATED CONTRACTIONS, SARCOPLASMIC-RETICULUM CA2+ CONTENT AND MEMBRANE CURRENT IN ISOLATED RAT VENTRICULAR MYOCYTES

1. The effects of tetracaine were examined on rat ventricular myocytes . In both field-stimulated and voltage-clamped cells tetracaine (100-2 00 mu M) 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 t ransient decrease of contraction produced by tetracaine was accompanie d by a small transient increase in the integral of the L-type Ca2+ cur rent and a larger transient decrease of the Na+-Ca2+ exchange current on repolarization. These are attributed to decreased systolic release of Ca2+. On removal of tetracaine there was an increase of the Na+-Ca2 + exchange current. Before the addition of tetracaine, calculated Ca2 influx and efflux across the sarcolemma were approximately equal. On adding tetracaine, efflux was transiently less than influx and, on rem oval of tetracaine, efflux was greater than influx. 3. These changes i n Ca2+ fluxes result in an increase of cell Ca2+ during exposure to te tracaine. The calculated magnitude of this increase was equal to that measured directly by applying caffeine (20 mM) to release sarcoplasmic reticulum (SR) Ca2+ and integrating the resulting Na+-Ca2+ exchange c urrent. 4. It is concluded that the effects of tetracaine can be accou nted for by depression of calcium-induced Ca2+ release (CICR). The res ponse is transient because the inhibition is compensated for by an inc rease of SR Ca2+ content such that there is' no steady-state effect on the magnitude of the systolic Ca2+ transient. The consequences of thi s result for the effects of other modulators of CICR are discussed.