TY - JOUR
T1 - The lifetime of inositol 1,4,5-trisphosphate in single cells
AU - Wang, Samuel S.H.
AU - Alousi, Adawia A.
AU - Thompson, Stuart H.
PY - 1995/1
Y1 - 1995/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028926595&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028926595&partnerID=8YFLogxK
U2 - 10.1085/jgp.105.1.149
DO - 10.1085/jgp.105.1.149
M3 - Article
C2 - 7730788
AN - SCOPUS:0028926595
SN - 0022-1295
VL - 105
SP - 149
EP - 171
JO - Journal of General Physiology
JF - Journal of General Physiology
IS - 1
ER -