Inositol trisphosphate and calcium oscillations

InsP₃ has two important functions in generating Ca²⁺ oscillations. It releases Ca²⁺ from the internal store and it can contribute to Ca²⁺ entry. A hypothesis has been developed to describe a mechanism for Ca²⁺ oscillations with particular emphasis on the way agonist concentration regulates oscillator frequency. The main idea is that the InsP₃ receptors are sensitized to release Ca²⁺ periodically by cyclical fluctuations of Ca²⁺ within the lumen of the endoplasmic reticulum. Each time a pulse of Ca²⁺ is released, the luminal level of Ca²⁺ declines and has to be replenished before the InsP₃ receptors are resensitized to deliver the next pulse of Ca²⁺. It is this loading of the internal store that explains why frequency is sensitive to external Ca²⁺ and may also account for how variations in agonist concentration are translated into changes in oscillation frequency. Variations in agonist-induced entry of external Ca²⁺, which can occur through different mechanisms, determine the variable rates of store loading responsible for adjusting the sensitivity of the InsP₃ receptors to produce the periodic pulses of Ca²⁺. The Ca²⁺ oscillator is an effective analogue-to-digital converter in that variations in the concentration of the external stimulus are translated into a change in oscillator frequency.