Mechanisms underlying InsP3-evoked global Ca2+ signals in mouse pancreatic acinar cells.
In secretory epithelial cells, complex patterns of Ca2+ signals regulate physiological processes. How these patterns are generated is still not fully understood. In particular, the basis of global Ca2+ waves is not clear. We have studied regional differences in InsP3-evoked Ca2+ release in single mouse pancreatic acinar cells, using high-speed (approximately 90 frames s-1), high-sensitivity Ca2+ imaging combined with rapid (10 ms) spot photolysis (2 micrometer diameter) of caged InsP3. Within a single region we measured Ca2+ response latency and rate of rise to construct an InsP3 dose-response relationship. Spot InsP3 liberation in the secretory pole region consistently elicited a dose-dependent, rapid release of Ca2+. Spot InsP3 liberation in the basal pole region of approximately 50% of cells elicited a similar dose-response relationship but with a lower apparent InsP3 affinity than in the secretory pole. In the other cells, basal pole InsP3 liberation did not elicit active Ca2+ release, even at the highest stimulus intensities we employed, although these same cells did respond when the stimulus spot was moved to different regions. We conclude that in the basal pole active sites of rapid Ca2+ release have a lower functional affinity for InsP3 than those in the secretory pole and are spread out in discrete sites across the basal pole. These properties explain the propagation of Ca2+ waves across the basal pole that are only observed at higher stimulus levels.
Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, UK.
K E
KE
Fogarty
J F
JF
Kidd
D A
DA
Tuft
P
P
Thorn
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005456:Fluorescent Dyes; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007834:Lasers; D008297:Male; D051379:Mice; D018715:Microscopy, Video; D009930:Organic Chemicals; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D010782:Photolysis; D011930:Reaction Time / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology; D014466:Ultraviolet Rays
D003911:Dextrans; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C071336:calcium green; D012433:Ryanodine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium