The aim of this work was to investigate whether it is possible to remove arrhythmogenic Ca²⁺ release from the sarcoplasmic reticulum that occurs in calcium overload without compromising normal systolic release. Exposure of rat ventricular myocytes to isoproterenol (1 μmol/L) resulted in an increased amplitude of the systolic Ca²⁺ transient and the appearance of waves of diastolic Ca²⁺ release. Application of tetracaine (25 to 50 μmol/L) decreased the frequency or abolished the diastolic Ca²⁺ release. This was accompanied by an increase in the amplitude of the systolic Ca²⁺ transient. Cellular Ca²⁺ flux balance was investigated by integrating Ca²⁺ entry (on the L-type Ca²⁺ current) and efflux (on Na–Ca²⁺ exchange). Isoproterenol increased Ca²⁺ influx but failed to increase Ca²⁺ efflux during systole (because of the abbreviation of the duration of the Ca²⁺ transient). To match this increased influx the bulk of Ca²⁺ efflux occurred via Na–Ca²⁺ exchange during a diastolic Ca²⁺ wave. Subsequent application of tetracaine increased systolic Ca²⁺ efflux and abolished the diastolic efflux. The increase of systolic efflux in tetracaine resulted from both increased amplitude and duration of the systolic Ca²⁺ transient. In the presence of isoproterenol, those Ca²⁺ transients preceded by diastolic release were smaller than those where no diastolic release had occurred. When tetracaine was added, the amplitude of the Ca²⁺ transient was similar to those in isoproterenol with no diastolic release and larger than those preceded by diastolic release. We conclude that tetracaine increases the amplitude of the systolic Ca²⁺ transient by removing the inhibitory effect of diastolic Ca²⁺ release.