PARTIAL CALCIUM-RELEASE IN RESPONSE TO SUBMAXIMAL INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR ACTIVATION

Even a prolonged application of a submaximal dose of Ins(1,4,5)P-3 is unable to release the same amount of Ca2+ from the Ins(1,4,5)P-3-sensitive store as a higher dose of Ins(1,4,5)P-3. Low doses of Ins(1,4,5)P-3 therefore only induce a partial release of the stored Ca2+. In this review, we will focus on the mechanisms that may contribute to this behaviour. Molecular heterogeneity of the Ins(1,4,5)P-3 receptor can contribute to such behaviour if ail the gene products and alternatively spliced isoforms would have different functional properties and be located in different store units. We will show that the control of the Ins(1,4,5)P-3 receptor by luminal Ca2+ also contributes to the partial release behaviour; it can set the sensitivity of the Ins(1,4,5)P-3 receptor and the decreasing luminal Ca2+ concentration may inhibit further release while some Ca2+ is still left in the store. It is finally possible that the Ins(1,4,5)P-3 receptor may adapt to a maintained stimulus.