Ca2+ microdomains in smooth muscle

In smooth muscle, Ca2+ controls diverse activities including cell division, contraction and cell death. Of particular significance in enabling Ca2+ to perform these multiple functions is the cell's ability to localize Ca2+ signals to certain regions by creating high local concentrations of Ca2+ (microdomains), which differ from the cytoplasmic average. Microdomains arise from Ca2+ influx across the plasma membrane or release from the sarcoplasmic reticulum (SR) Ca2+ store. A single Ca2+ channel can create a microdomain of several micromolar near (∼200 nm) the channel. This concentration declines quickly with peak rates of several thousand micromolar per second when influx ends. The high [Ca2+] and the rapid rates of decline target Ca2+ signals to effectors in the microdomain with rapid kinetics and enable the selective activation of cellular processes. Several elements within the cell combine to enable microdomains to develop. These include the brief open time of ion channels, localization of Ca2+ by buffering, the clustering of ion channels to certain regions of the cell and the presence of membrane barriers, which restrict the free diffusion of Ca2+. In this review, the generation of microdomains arising from Ca2+ influx across the plasma membrane and the release of the ion from the SR Ca2+ store will be discussed and the contribution of mitochondria and the Golgi apparatus as well as endogenous modulators (e.g. cADPR and channel binding proteins) will be considered.