The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease

Many cellular functions are regulated by calcium (Ca 2+ ) signals that are generated by different signaling pathways. One of these is the inositol 1,4,5-trisphosphate/calcium (InsP 3 /Ca 2+ ) signaling pathway that operates through either primary or modulatory mechanisms. In its primary role, it generates the Ca 2+ that acts directly to control processes such as metabolism, secretion, fertilization, proliferation, and smooth muscle contraction. Its modulatory role occurs in excitable cells where it modulates the primary Ca 2+ signal generated by the entry of Ca 2+ through voltage-operated channels that releases Ca 2+ from ryanodine receptors (RYRs) on the internal stores. In carrying out this modulatory role, the InsP 3 /Ca 2+ signaling pathway induces subtle changes in the generation and function of the voltage-dependent primary Ca 2+ signal. Changes in the nature of both the primary and modulatory roles of InsP 3 /Ca 2+ signaling are a contributory factor responsible for the onset of a large number human diseases.