Local and global Ca2+ signals from voltage-dependent Ca2+ channels (VDCCs) and ryanodine-sensitive Ca2+ release (RyRs) channels in the sarcoplasmic reticulum (SR) encode information to different Ca2+-sensitive targets including the large- (BK) and small-conductance (SK) Ca2+-activated K+ channels in the surface membrane. In smooth muscle, unlike cardiac muscle, Ca2+ signalling to RyRs is not local, exhibiting a significant lag between VDCC activation and subsequent RyR stimulation, measured as Ca2+ sparks and associated BK currents. However, Ca2+ signalling from RyRs (Ca2+ sparks) to BK channels appears to be local in arterial (ASM) and urinary bladder smooth muscle (UBSM), consistent with a close proximity of SR RyRs to BK channels. The response of BK channels in ASM and UBSM depends on the tuning of the Ca2+/voltage sensitivity of the BK channel by its accessory subunit, the beta1 subunit. UBSM, in contrast to ASM, has both BK and SK channels. SK channels in UBSM are solely activated by Ca2+ signals from VDCCs, whereas BK channels are activated by Ca2+ from both VDCCs and RyRs. The differential regulation of BK and SK channels by Ca2+ signals underlies their roles in regulating action potential duration and membrane potential (BK channels) and after-hyperpolarizations (SK channels) in smooth muscle.