The sarcoplasmic reticulum: then and now.

Structural and functional studies indicate the important role of the sarcoplasmic reticulum (SR) in excitation-contraction coupling in smooth and striated muscles, as well as a similar Ca2+ signalling function of the endoplasmic reticulum (ER) in non-muscle cells. Electron probe analysis directly established the SR/ER of smooth muscle as a sink and source of Ca2+, while immunoelectron and immunofluorescence microscopy showed both inositol-1,4,5-trisphosphate (InsP3) and ryanodine receptors localized to its membranes. Structural relationships, some yet to have fully determined functions, occur between the mitochondria and the SR, and the junctional SR and plasma membrane. Ca2+ is released by stimuli that generate InsP3 indicating the primary role of InsP3 receptors in Ca2+-release in smooth, although not in striated, muscle. Pathological mitochondrial Ca2+ uptake occurs at high [Ca2+]i similarly in both muscle and non-muscle cells. Based on newer evidence, earlier experimental results obtained with fluorescent Ca2+ indicators and related to phasic and tonic components of contraction can now be reinterpreted. Electron energy loss spectroscopy for high-resolution Ca2+ imaging and flash photolysis of caged agonists for exploration of the rapid kinetics of Ca2+ release from the SR are currently being explored.