It is generally agreed that in spite of the functional diversity in the control of contractile activity of smooth muscle at structural, myogenic, neurogenic, and hormonal levels, the final common pathway of these control functions is the regulation of cytoplasmic calcium ion (Ca2+) concentration in the smooth muscle cell. The source of Ca2+ available to initiate excitation-contraction coupling in smooth muscles may be extracellular as well as intracellular depending upon the source of smooth muscle, cellular environment, and the nature of stimulus. Thus, the increase of cytoplasmic concentration of Ca2+ for contraction may be achieved by the influx of Ca2+ via Ca2+ channels that open upon depolarization (electromechanical coupling via voltage-dependent Ca2+ channels) or receptor occupancy (pharmaco-mechanical coupling via receptor-operated Ca2+ channels) or alternatively by the release of intracellularly sequestered Ca2+. For the initiation and maintenance of the state of relaxation after each contraction, inhibition of Ca2+ influx or release would not be adequate in lowering cytoplasmic Ca2+ contraction to 10−7M or less because of the residual inward leak of Ca2+ across the cell membrane. A mechanism for extrusion or sequestration of the cytoplasmic Ca2+ must therefore be operative to lower the Ca2+ concentration. Plasma membrane, endoplasmic reticulum, and mitochondria have been proposed as the major Ca2+ sequestering sites based upon direct evidence derived from ultrastructural studies (see Chapter 1) and studies using isolated subcellular membranes (see Chapters 10 and 11). Clearly, intracellular Ca2+ ions are compartmentalized in all smooth muscles, but the relative importance of the roles of various Ca2+ compartments during excitation-contraction-relaxation cycles in smooth muscle has been and still is a debating issue (23, 63).
