SPONTANEOUS OSCILLATIONS OF INTRACELLULAR CALCIUM IN SINGLE BOVINE PARATHYROID CELLS MAY BE ASSOCIATED WITH THE INHIBITION OF PARATHYROID-HORMONE SECRETION

PTH secretion is tightly regulated by extracellular calcium ([Ca2+](e) ) and in turn regulates calcium homeostasis through its action on targ et tissues. We investigated the mechanism and physiological significan ce of intracellular calcium ([Ca2+](i)) levels in relation to the secr etion of PTH in single bovine parathyroid cells. [Ca2+](i) was recorde d using digital imaging microscopy, and secretion of PTH was correlate d in the same cell using the reverse hemolytic plaque assay. In indivi dual parathyroid cells, oscillations of[Ca2+](i) were present in respo nse to specific stimuli. Like secretory activity, response to [Ca2+](e ) concentrations was heterogeneous. Oscillations of[Ca2+](i) occurred spontaneously in 22% of cells at inhibitory concentrations of [Ca2+](e ). Oscillations were present only in high [Ca2+](e) (greater than or e qual to 1.8 mM) and not noted at lower concentrations of[Ca2+](e). The interval and amplitude of[Ca2+](i) oscillations were 42 +/- 2 sec, an d 20 +/- 1 nM (mean +/- SE), respectively. Oscillations were rapidly a bolished when [Ca2+](e) was removed by EGTA, and this effect was rever sible. Addition of Mg2+ or polycationic antibiotics such as neomycin r esulted in an [Ca2+](i) spike, but oscillations were absent. Lanthanum , which blocks Ca2+ influx through calcium channels in various cells, rarely caused oscillations even in the presence of high concentrations of[Ca2+](e). To test the role of cAMP in [Ca2+](i) oscillations, we a dded the beta-agonist isoproterenol. The addition of isoproterenol, ho wever, did not cause oscillations. The number of cells that released P TH was significantly lower in cells with oscillations compared with ce lls without oscillations. We suggest that spontaneous [Ca2+](i) oscill ations are due to the influx of [Ca2+](e) through ion channels rather than release from [Ca2+](i) stores and may be a specific intracellular signal associated with inhibition of PTH secretion.