Using a confocal microscope discrete foci of elevated intracellular Ca2+ concentration ([Ca2+]i), called "Ca2+ sparks", were observed in cardiac, skeletal and vascular smooth muscle cells. In all three muscle types Ca2+ sparks could be attributed to the opening of a single (or a few) ryanodine receptors (RyR). Simultaneous measurement of whole-cell Ca2+ currents (ICa) and Ca2+ sparks in rat ventricular myocytes showed that the probability of Ca2+ spark occurrence (Ps) depends on the square of iCa. Furthermore, it was found that at negative potentials the opening of a single L-type Ca2+ channel can provide enough Ca2+ to activate a single Ca2+ spark by the mechanism of calcium-induced calcium-release (CICR). In skeletal muscle fibers, however, Ca2+ sparks were activated by the voltage-sensor and by CICR. In marked contrast to striated muscle Ca2+ sparks were found to hyperpolarize and relax myogenic cerebral arteries because Ca2+ sparks occupied a small volume of the cell (0.8%), had at low frequency (about 1 Hz), and in occurred close to the sarcolemma were they could activate hyperpolarizing Ca2+-activated potassium (KCa) currents.