Cell type-specific modes of feedback regulation of capacitative calcium entry

The Ca2+ ATPase inhibitor, thapsigargin, activated Ca2+ entry into pancreatic acinar cells, a process known as capacitative calcium entry, In cells loaded with the calcium chelator BAPTA, the transient Ca2+ release was blunted and the rise of [Ca2+](i) on readdition of Ca2+ was slowed, However, the steady-state [Ca2+](i) due to Ca2+ entry was substantially augmented compared with control cells, This indicates that [Ca2+](i) exerts a negative feedback on Ca2+ entry from a compartment buffered by BAPTA and separated from the bulk of cytoplasmic Ca2+. This interaction probably occurs close to the calcium channel where [Ca2+] is higher than in the bulk of the cytoplasm, In support of this interpretation, the slower Ca2+ chelator, EGTA, also blunted the release of Ca2+ and slowed the rise of the sustained [Ca2+](i) phase but failed to augment steady-state [Ca2+](i). In contrast, Ca2+ entry in NIH 3T3 cells was characterized by a transient rise of [Ca2+](i) that decays to near prestimulus levels, This decay in Ca2+ entry also results from negative feedback by Ca2+ because the decrease in Ca2+ entry was reversed by incubation in a Ca2+ deficient medium, However, unlike its effects in acinar cells, BAPTA neither augmented steady-state [Ca2+](i) nor pre vented the inactivation of entry, Rather, in BAPTA-loaded cells, [Ca2+](i) failed to increase substantially suggesting that negative regulation by Ca2+ may occur at a site distinct from the cytoplasmic compartment and inaccessible to cytoplasmic BAPTA, These two distinct types of feedback behavior may indicate subtypes of store-operated calcium channels expressed in different cells or a single type of channel which is differentially regulated in a cell type-specific manner.