In Cardiac excitation-contraction coupling, Ca²⁺-induced Ca²⁺ release (CICR) from ryanodine receptors (RyRs), triggered by Ca²⁺ entry through the nearby L-type Ca²⁺ channel, induces the Ca²⁺-dependent inactivation (CDI) of the Ca²⁺ channel. Aiming at elucidating the physiological role of CDI produced by CICR (CICR-dependent CDI), we investigated the contribution of the CICR-dependent CDI to action potential (AP) waveform and the amount of Ca²⁺-influx through Ca²⁺ channels during AP in rat ventricular myocytes. The elimination of the CICR-dependent CDI, by depletion of the SR Ca²⁺ with thapsigargin, significantly prolonged AP duration (APD). APD changed in parallel with the magnitude of CICR during the recovery of the SR Ca²⁺ content after transient depletion by caffeine. Such CICR-dependent change of APD persisted under the highly Ca²⁺ buffered condition where the Ca²⁺ signaling was restricted to nanoscale domains. Blockers of the Ca²⁺-dependent Cl^- channel or the BK channel did not affect AP waveform. The amount of Ca²⁺-influx through Ca²⁺ channels during the SR-depleted type AP waveform, measured in the SR-depleted myocyte, was increased by 40% over that during the SR-intact type AP waveform measured in the SR-intact myocyte. The PKA-stimulation further enhanced the Ca²⁺-influx during AP under the SR-depleted condition to 70% over that under the SR-intact condition. These results indicate that the CICR-dependent CDI of L-type Ca²⁺ channels, under control of the privileged cross-signaling between L-type Ca²⁺ channels and RyRs, plays important roles for monitoring and tuning the SR Ca²⁺ content via changes of AP waveform and the amount of Ca²⁺-influx during AP in ventricular myocytes.