The hypothesis that Na⁺ influx during the action potential (AP) activates reverse Na⁺–Ca²⁺ exchange (NCX) and subsequent entry of trigger Ca²⁺ is controversial. We tested this hypothesis by monitoring intracellular Ca²⁺ before and after selective inactivation of I_Na prior to a simulated action potential in patch‐clamped ventricular myocytes isolated from adult wild‐type (WT) and NCX knockout (KO) mice. First, we inactivated I_Na using a ramp prepulse to −45 mV. In WT cells, inactivation of I_Na decreased the Ca²⁺ transient amplitude by 51.1 ± 4.6% (P < 0.001, n= 14) and reduced its maximum release flux by 53.0 ± 4.6% (P < 0.001, n= 14). There was no effect on diastolic Ca²⁺. In striking contrast, Ca²⁺ transients in NCX KO cardiomyocytes were unaffected by the presence or absence of I_Na (n= 8). We obtained similar results when measuring trigger Ca²⁺ influx in myocytes with depleted sarcoplasmic reticulum. In WT cells, inactivation of I_Na decreased trigger Ca²⁺ influx by 37.8 ± 6% and maximum rate of flux by 30.6 ± 7.7% at 2.5 mm external Ca²⁺ (P < 0.001 and P < 0.05, n= 9). This effect was again absent in the KO cells (n= 8). Second, exposure to 10 μm tetrodotoxin to block I_Na also reduced the Ca²⁺ transients in WT myocytes but not in NCX KO myocytes. We conclude that I_Na and reverse NCX modulate Ca²⁺ release in murine WT cardiomyocytes by augmenting the pool of Ca²⁺ that triggers ryanodine receptors. This is an important mechanism for regulation of Ca²⁺ release and contractility in murine heart.