[CA2-ACTIVATED CA2+ INFLUX UNDERLIES AGONIST-INDUCED AND THAPSIGARGIN-INDUCED [CA2+](I) OSCILLATIONS IN SALIVARY SALIVARY ACINAR-CELLS(](I)INHIBITION OF CA2+ RELEASE)

Inhibition of sarcoplasmic/endoplasmic reticulum Ca2+-ATPases by thaps igargin elicits [Ca2+](i) oscillations in rat salivary gland (parotid) acinar cells which are similar to those activated by agonists but are neverthe less independent of inositol 1,4,5-trisphosphate (IP3) or IP 3-sensitive Ca2+ stoves (Foskett, J,K., Roifman, C, M,, and Wong, D, ( 1991) J. Biol; Chem, 266, 2778-2782), Neither bafilomycin alone or tog ether 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 Ca2+-ATPase by 1 mM La3+ inhibited the d ecline 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 immediat ely abolished oscillations, even when applied during the [Ca2+](i) ris ing phase of the cycle, Ca2+ influx rate oscillated during [Ca2+](i) o scillations, varying 1.5-13-fold during a cycle, Modification of the r ate of Ca2+ influx, by titrating the extent of depletion of IP3-sensit ive stores or manipulating extracellular [Ca2+], indicated that oscill ations depended on a high rate of Ca2+ influx. In thapsigargin- or car bachol-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 [C a2+](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,