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 N1E-115 neuroblastoma cells. Ca release followed receptor activation after a latency of 0.4 to 20 s. 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.
Wang
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Neurosciences Program, Stanford University, Pacific Grove, California 93950, USA.
Alousi
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Thompson
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000187:drug effects / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D016257:Fura-2; D006207:Half-Life; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000252:Calcium-Transporting ATPases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016257:Fura-2