CELL-TYPE-SPECIFIC MODES OF FEEDBACK-REGULATION OF CAPACITATIVE CALCIUM-ENTRY

The Ca2+ ATPase inhibitor, thapsigargin, activated Ca2+ entry into pan creatic acinar cells, a process known as capacitative calcium entry, I n cells loaded with the calcium chelator BAPTA, the transient Ca2+ rel ease was blunted and the rise of [Ca2+](i) on readdition of Ca2+ was s lowed, However, the steady-state [Ca2+](i) due to Ca2+ entry was subst antially augmented compared with control cells, This indicates that [C a2+](i) exerts a negative feedback on Ca2+ entry from a compartment bu ffered 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 interp retation, the slower Ca2+ chelator, EGTA, also blunted the release of Ca2+ and slowed the rise of the sustained [Ca2+](i) phase but failed t o augment steady-state [Ca2+](i). In contrast, Ca2+ entry in NIH 3T3 c ells was characterized by a transient rise of [Ca2+](i) that decays to near prestimulus levels, This decay in Ca2+ entry also results from n egative feedback by Ca2+ because the decrease in Ca2+ entry was revers ed by incubation in a Ca2+ deficient medium, However, unlike its effec ts 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 re gulation by Ca2+ may occur at a site distinct from the cytoplasmic com partment and inaccessible to cytoplasmic BAPTA, These two distinct typ es of feedback behavior may indicate subtypes of store-operated calciu m channels expressed in different cells or a single type of channel wh ich is differentially regulated in a cell type-specific manner.