Dual Regulation of Calcium Mobilization by Inositol 1,4,5-Trisphosphate in a Living Cell

Abstract

Changes in cytosolic free calcium ([Ca2+]i) often take the form of a sustained response or repetitive oscillations. The frequency and amplitude of [Ca2+]i oscillations are essential for the selective stimulation of gene expression and for enzyme activation. However, the mechanism that determines whether [Ca2+]i oscillates at a particular frequency or becomes a sustained response is poorly understood. We find that [Ca2+]i oscillations in rat megakaryocytes, as in other cells, results from a Ca2+-dependent inhibition of inositol 1,4,5-trisphosphate (IP3)–induced Ca2+ release. Moreover, we find that this inhibition becomes progressively less effective with higher IP3 concentrations. We suggest that disinhibition, by increasing IP3 concentration, of Ca2+-dependent inhibition is a common mechanism for the regulation of [Ca2+]i oscillations in cells containing IP3-sensitive Ca2+ stores.

Altered Organelle Calcium Transport in Ovarian Physiology and Cancer

“…Both the rate and magnitude of intracellular calcium spikes are involved in essential molecular processes such as gene expression [ 89 ] and enzyme activation [ 90 ]. While it has long been shown that a steady increase in the frequency of calcium oscillations may lead to a sustained rise in intracellular Ca 2+ [ 91 , 92 ], the exact mechanism underlying the augmented frequency of Ca 2+ transients is yet to be elucidated [ 93 ]. Furthermore, although calcium spikes have been described at length in electrically excitable cells such as muscle (smooth, skeletal, cardiac) or neuronal cells, the same cannot be said for epithelial cells.…”