Ca2+ dynamics in salivary acinar cells: distinct morphology of the acinar lumen underlies near-synchronous global Ca2+ responses.
In salivary acinar cells, the pattern of the Ca2+ signals that regulates fluid and enzyme secretion has yet to be resolved, as there are conflicting reports in the literature. We have used a two-photon technique to directly visualize the acinar cell lumen in living fragments of exocrine tissue and simultaneously recorded agonist-induced changes in intracellular Ca2+. We show near-synchronous global Ca2+ responses in submandibular acinar cells, distinct from the typical apical to basal Ca2+ wave usually seen in rodent pancreatic acinar cells. In an effort to explain the basis of these near-synchronous global Ca2+ responses we used immunocytochemical experiments to localize luminal proteins and inositol trisphosphate receptors (InsP3Rs) in tissue fragments. Zona occludens 1 (ZO-1), a tight junction protein, shows that individual submandibular acinar cells are often nearly completely encircled by a narrow luminal structure. By contrast, in pancreatic fragments, ZO-1 staining shows short luminal branches terminating abruptly at the apical pole of single acinar cells. Co-immunostaining of InsP3Rs type 2 and type 3 showed them in the same region as ZO-1 in both exocrine tissues. Functional experiments showed that the near-synchronous global Ca2+ responses were still observed in the absence of extracellular Ca2+ and also in the presence of ryanodine. We conclude that the elaborate luminal region of submandibular cells leads to a hitherto unrecognized extensive distribution of InsP3Rs in a band around the cell and that this underlies the near-synchronous global Ca2+ response to agonists. We suggest that this may be a structural adaptation in submandibular cells to support the copious amounts of fluid secreted.
Larina
Olga
O
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Thorn
Peter
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D018613:Microscopy, Confocal; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology / Q000378:metabolism*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002118:Calcium