Physiology of intracellular calcium buffering

Abstract

Calcium signalling underlies much of physiology. Almost all the Ca 2+ in the cytoplasm is bound to buffers, with typically only about 1% being freely ionized at resting levels in most cells. Physiological Ca 2+ buffers include small molecules and proteins, and experimentally, Ca 2+ indicators will also buffer calcium. The chemistry of interactions between Ca 2+ and buffers determines the extent and speed of Ca 2+ binding. The physiological effects of Ca 2+ buffers are determined by the kinetics with which they bind Ca 2+ and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca 2+ , the Ca 2+ concentration, and whether Ca 2+ ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca 2+ signals as well as changes of Ca 2+ concentration in organelles. It can also facilitate Ca 2+ diffusion inside the cell. Ca 2+ buffering affects synaptic transmission, muscle contraction, Ca 2+ transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation, tetanic contraction in skeletal muscle, and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca 2+ buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.