The lifetime of inositol 1,4,5-trisphosphate in single cells

In many eukaryotic cell types, receptor activation leads to the formation of inositol 1,4,5-trisphosphate (IP₃) which causes calcium ions (Ca) to be released from internal stores. Ca release was observed in response to the muscarinic agonist carbachol by fura-2 imaging of NIE-115 neuroblastoma cells. Ca release followed receptor activation after a latency of 0.4 to 20s. Latency was not caused by Ca feedback on IP₃ receptors, but rather by IP₃ accumulation to a threshold for release. The dependence of latency on carbachol dose was fitted to a model in which IP₃ synthesis and degradation compete, resulting in gradual accumulation to a threshold level at which Ca release becomes regenerative. This analysis gave degradation rate constants of IP₃ in single cells ranging from 0 to 0.284 s^-1 (0.058 ± 0.067 s^-1 SD, 53 cells) and a mean IP₃ lifetime of 9.2 ± 2.2 s. IP₃ degradation was also measured directly with biochemical methods. This gave a half life of 9 ± 2 s. The rate of IP₃ degradation sets the time frame over which IP₃ accumulations are integrated as input signals. IP₃ levels are also filtered over time, and on average, large-amplitude oscillations in IP₃ in these cells cannot occur with period <10 s.