Perturbation of myo-inositol-1,4,5-trisphosphate levels during agonist-induced Ca2+ oscillations
Details
Serval ID
serval:BIB_33F653B0EBF1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Perturbation of myo-inositol-1,4,5-trisphosphate levels during agonist-induced Ca2+ oscillations
Journal
Biophysical Journal
ISSN
0006-3495 (Print)
Publication state
Published
Issued date
01/1998
Volume
74
Number
1
Pages
523-31
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
Agonist-induced Ca2+ oscillations in rat hepatocytes involve the production of myo-inositol-1,4,5-trisphosphate (IP3), which stimulates the release of Ca2+ from intracellular stores. The oscillatory frequency is conditioned by the agonist concentration. This study investigated the role of IP3 concentration in the modulation of oscillatory frequency by using microinjected photolabile IP3 analogs. Photorelease of IP3 during hormone-induced oscillations evoked a Ca2+ spike, after which oscillations resumed with a delay corresponding to the period set by the agonists. IP3 photorelease had no influence on the frequency of oscillations. After photorelease of 1-(alpha-glycerophosphoryl)-D-myo-inositol-4,5-diphosphate (GPIP2), a slowly metabolized IP3 analog, the frequency of oscillations initially increased by 34% and declined to its original level within approximately 6 min. Both IP3 and GPIP2 effects can be explained by their rate of degradation: the half-life of IP3, which is a few seconds, can account for the lack of influence of IP3 photorelease on the frequency, whereas the slower metabolism of GPIP2 allowed a transient acceleration of the oscillations. The phase shift introduced by IP3 is likely the result of the brief elevation of Ca2+ during spiking that resets the IP3 receptor to a state of maximum inactivation. A mathematical model of Ca2+ oscillations is in satisfactory agreement with the observed results.
Keywords
Animals
Calcium/*metabolism
Cells, Cultured
Computer Simulation
Cytosol/metabolism
Inositol 1,4,5-Trisphosphate/*metabolism
Inositol Phosphates/administration & dosage/pharmacokinetics/pharmacology
Kinetics
Liver/cytology/drug effects/*metabolism
Male
Mathematics
Microinjections
Models, Biological
Oscillometry
Phenylephrine/*pharmacology
Photolysis
Rats
Rats, Wistar
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:08
Last modification date
20/08/2019 14:20