Sarcoplasmic reticulum, calcium waves and myometrial signalling.

Ca2+ waves are rises of intracellular free Ca2+ that occur in a temporally and spatially coordinated manner, such that a leading edge of a wave front can be clearly discerned. Waves that occur within the bounds of a single cell are termed intracellular Ca2+ waves. Generation of a Ca2+ wave may be the end result of multiple cellular signalling events and, consequently, is a mechanism of signal integration or information processing. Passage of a Ca2+ wave is a mechanism for signalling within a cell, or across a cell. This paper reviews intracellular Ca2+ waves and their relationship with the sarcoplasmic reticulum (SR) in uterine smooth muscle. Wave speeds are the rate at which the leading front of the Ca2+ wave travels, and are measured by time-lapse imaging of Ca2+-dependent fluorescent dyes. Waves can be experimentally generated in cultured cells by agonist or mechanical stimulation. Wave speeds are unaffected by the removal of Ca2+ in the bathing solution, indicating that the source of the Ca2+ is the SR. The mechanisms of intracellular wave propagation can be investigated by modulating the Ca2+ release mechanisms of the SR. The mechanism most consistent with our observations is that propagation of intracellular Ca2+ waves in cultured human uterine myocytes is SR Ca2+ release that can utilize InsP3 receptors alone, Ca2+-induced Ca2+ release receptors alone, or both together. The rate-determining step for Ca2+ wave propagation is diffusion of Ca2+ through a highly buffered cytoplasm. Passage of a Ca2+ wave also results in capacitative Ca2+ entry, which links deep cytoplasmic Ca2+ changes to subplasmalemmal Ca2+ concentrations.