Ca2+ oscillations in pancreatic acinar cells: spatiotemporal relationships and functional implications.
The pancreatic acinar cells are of particular interest for the study of cytosolic Ca2+ signals, since they are morphologically polarized and generate agonist-specific Ca2+ oscillation patterns. Recent data obtained by combining digital video imaging of Fura-2 fluorescence with patch-clamp whole-cell current recording have provided new information on the spatiotemporal relationships of the cytosolic Ca2+ signals and the Ca(2+)-activated ionic currents. Low agonist concentrations evoke repetitive short-lasting local Ca2+ spikes in the secretory pole region that activate shortlasting current spikes. In the case of acetylcholine stimulation the spikes are confined to this region. When cholecystokinin is used the shortlasting local spikes precede longer Ca2+ transients that spread to the whole of the cell. Infusion of non-metabolizable inositol trisphosphate analogues can mimic these responses. The shortlasting local Ca2+ spikes are particularly sensitive to blockade by the inositol trisphosphate receptor antagonist heparin. These results show that the secretory pole region has a particularly high sensitivity to inositol trisphosphate probably due to clustering of high affinity receptors.
Thorn
P
P
Physiological Laboratory, University of Liverpool, UK.
Lawrie
A M
AM
Smith
P M
PM
Gallacher
D V
DV
Petersen
O H
OH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008564:Membrane Potentials; D008954:Models, Biological; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013997:Time Factors
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013438:Sulfhydryl Compounds; C058451:JMV 180; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D002766:Cholecystokinin; D012844:Sincalide; D000109:Acetylcholine; D002118:Calcium