[Ca2+]i inhibition of Ca2+ release-activated Ca2+ influx underlies agonist- and thapsigargin-induced [Ca2+]i oscillations in salivary acinar cells.
Inhibition of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases by thapsigargin elicits [Ca2+]i oscillations in rat salivary gland (parotid) acinar cells which are similar to those activated by agonists but are nevertheless independent of inositol 1,4,5-trisphosphate (IP3) or IP3-sensitive Ca2+ stores (Foskett, J. K., Roifman, C. M., and Wong, D. (1991) J. Biol. Chem. 266, 2778-2782). Neither bafilomycin alone or together with monensin or chloroquine inhibited thapsigargin-induced [Ca2+]i oscillations, ruling out the involvement of vacuolar-type proton pumps or organellar acidity in the mechanisms underlying them. Acute inhibition of plasma membrane Ca(2+)-ATPase by 1 mM La3+ inhibited the decline of [Ca2+]i during the falling phase of the oscillation. Acute inhibition of plasma membrane Ca2+ influx by removal of extracellular Ca2+, membrane depolarization, or inorganic channel blockers immediately abolished oscillations, even when applied during the [Ca2+]i rising phase of the cycle. Ca2+ influx rate oscillated during [Ca2+]i oscillations, varying 1.5-13-fold during a cycle. Modification of the rate of Ca2+ influx, by titrating the extent of depletion of IP3-sensitive stores or manipulating extracellular [Ca2+], indicated that oscillations depended on a high rate of Ca2+ influx. In thapsigargin- or carbachol-treated cells which did not exhibit a sustained [Ca2+]i rise or [Ca2+]i oscillations, inhibition of Ca2+ influx activated plasma membrane Ca2+ permeability. Thus, agonist- and thapsigargin-induced [Ca2+]i oscillations in parotid acinar cells appear to be generated by plasma membrane-based mechanisms which involve periodic inactivation by [Ca2+]i of the Ca2+ release-activated Ca2+ influx pathway.
Foskett
J K
JK
Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Wong
D C
DC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010507:Periodicity; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012469:Salivary Glands / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D002121:Calcium Channel Blockers; D013729:Terpenes; D019284:Thapsigargin; D007811:Lanthanum; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium