A sodium/calcium exchange mechanism that mediates both Ca2+ exit and Ca2+ entry is present in the sarcolemma of most types of muscle including mammalian cardiac muscle and vascular smooth muscle (VSM). The rate and direction of Ca2+ transport mediated by the exchanger are normally regulated primarily by: (a) the intracellular free Ca2+ concentration (since both Ca2+ entry and exit are activated by intracellular Ca2+), (b) the intracellular Na+, and (c) the absolute difference between the membrane potential and the exchanger reversal potential. In both cardiac muscle and VSM, the exchanger biases the level of [Ca2+]i and thereby controls the amount of Ca2+ stored in the sarcoplasmic reticulum and, thus, the amount available for release when the cells are activated. In both tissues, the exchanger also plays an important role in the extrusion of Ca2+ following contractile activation.