We tested the hypothesis that local and tight coupling between the Cav 1.2 channels and RyRs is not required to initiate Ca2+ sparks in VSMC. Cross-signaling between Cav1.2 channels and RyR was studied using an approach based on Poisson statistical analysis of elementary calcium release events (ECRE). ECRE were recorded as Ca2+ sparks or STOCs in tibial VSMCs of smooth muscle-specific L-type Cav 1.2 channel knockout (SMAKO) mice. Cav1.2 channel gene inactivation reduced Ca2+ spark frequency and amplitude by >50%. The first-latency histograms of sparks only slightly depended on the depolarization level and peaked at a relatively positive potential in wild-type VSMCs, i.e., ~+20 mV. Furthermore, average latencies between - 30 mV and +50 mV occurred at > 100 ms. Average latency of the first identified STOCs was similar and >100 ms in wild-type, nimodipine-treated and SMAKO VSMC. First-latency and all- latency histograms had different waveforms which imply that the release is not determined by the time course of first event activation, with relatively fewer re-openings, as is the case in skeletal and cardiac muscle. Thus, Cav1.2 channels are important for generation of VSMC Ca2+ sparks. However, local and tight coupling between the Cav1.2 channels and RyRs is not required to initiate Ca2+ sparks from single CRUs in arterial VSMC.