A prototypical example of local Ca2+ signaling is Ca2+ sparks and spontaneous transient outward current (STOC) in smooth muscle and neurons (Brown et al., 1983; Nelson et al., 1995; Bolton and Imaizumi, 1996). Ca2+ sparks are highly localized, short-lived Ca2+ transients because of the opening of RYRs on the membrane of endo/sarcoplasmic reticulum. In smooth muscle cells, Ca2+ sparks activate large-conductance Ca2+-activated K+ (BK) channels to give rise to STOCs. Depending on the type of smooth muscle, spark-STOC signaling renders a different physiological function. In vascular smooth muscle from the cerebral artery, functional coupling of sparks to STOCs hyperpolarizes the membrane potential, which in turn shuts off voltage-dependent Ca channels (VDCCs), leading to the decrease in global [Ca2+] and relaxation (Nelson et al., 1995). In ureteral smooth muscle, the activation of STOCs by Ca2+ sparks limits the availability of VDCCs, resulting in a prolonged action potential refractory period (Burdyga and Wray, 2005). Finally, because of their capability to also turn on spontaneous transient inward currents (STICs), which counteracts the STOC, Ca2+ sparks serve as a membrane potential stabilizer in smooth
