Kinetic control of multiple forms of Ca(2+) spikes by inositol trisphosphate in pancreatic acinar cells.
The mechanisms of agonist-induced Ca(2+) spikes have been investigated using a caged inositol 1,4,5-trisphosphate (IP(3)) and a low-affinity Ca(2+) indicator, BTC, in pancreatic acinar cells. Rapid photolysis of caged IP(3) was able to reproduce acetylcholine (ACh)-induced three forms of Ca(2+) spikes: local Ca(2+) spikes and submicromolar (<1 microM) and micromolar (1-15 microM) global Ca(2+) spikes (Ca(2+) waves). These observations indicate that subcellular gradients of IP(3) sensitivity underlie all forms of ACh-induced Ca(2+) spikes, and that the amplitude and extent of Ca(2+) spikes are determined by the concentration of IP(3). IP(3)-induced local Ca(2+) spikes exhibited similar time courses to those generated by ACh, supporting a role for Ca(2+)-induced Ca(2+) release in local Ca(2+) spikes. In contrast, IP(3)- induced global Ca(2+) spikes were consistently faster than those evoked with ACh at all concentrations of IP(3) and ACh, suggesting that production of IP(3) via phospholipase C was slow and limited the spread of the Ca(2+) spikes. Indeed, gradual photolysis of caged IP(3) reproduced ACh-induced slow Ca(2+) spikes. Thus, local and global Ca(2+) spikes involve distinct mechanisms, and the kinetics of global Ca(2+) spikes depends on that of IP(3) production particularly in those cells such as acinar cells where heterogeneity in IP(3) sensitivity plays critical role.
Ito
K
K
Department of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Miyashita
Y
Y
Kasai
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D002021:Buffers; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects*; D003374:Coumarins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D018613:Microscopy, Confocal; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010782:Photolysis; D013844:Thiazoles / Q000378:metabolism
D052160:Benzothiazoles; D002021:Buffers; D003374:Coumarins; D005456:Fluorescent Dyes; D013844:Thiazoles; C104515:benzothiazole coumarin; C061868:inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; D002118:Calcium