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 target tissues. We investigated the mechanism and physiological significance of intracellular calcium ([Ca2+](i)) levels in relation to the secretion of PTH in single bovine parathyroid cells. [Ca2+](i) was recorded using digital imaging microscopy, and secretion of PTH was correlated in the same cell using the reverse hemolytic plaque assay. In individual parathyroid cells, oscillations of[Ca2+](i) were present in response 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 equal 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, and 20 +/- 1 nM (mean +/- SE), respectively. Oscillations were rapidly abolished when [Ca2+](e) was removed by EGTA, and this effect was reversible. Addition of Mg2+ or polycationic antibiotics such as neomycin resulted 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 added the beta-agonist isoproterenol. The addition of isoproterenol, however, did not cause oscillations. The number of cells that released PTH was significantly lower in cells with oscillations compared with cells without oscillations. We suggest that spontaneous [Ca2+](i) oscillations 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.