Where is the "inverting factor" in hormone secretion from parathyroid cells?

Secretion of hormones and transmitters in the body fall into two general categories. In the majority of the secreting cells, including the presynaptic terminals in the nervous system, an increase in the extracellular calcium causes an increase in secretion (4, 9, 22, 23). There are two notable exceptions to this general rule: the parathyroid cells (3, 15) and the renal juxtaglomerular cells (5), where an increase in extracellular calcium leads to a decrease in secretion. Because these two cell types have a cardinal role in a wide variety of physiological and pathophysiological functions, it is of great importance to understand the regulation of their hormone secretion process. A key element to such an understanding is the identification of the location of the "inverting step, " which makes the parathyroid cells behave in a fashion contrary to most other secretory cells. Whole cell imaging studies strongly suggested that the inversion factor is between the changes in intracellular calcium concentration ([Ca ²⁺] _i) and the secretion of the hormone (24). Surprisingly, confocal calcium imaging of the parathyroid cells did not support this dogma. It revealed that the interior of the parathyroid cell is a nonhomogeneous medium and that an increase in the extracellular calcium concentration produces changes in [Ca ²⁺] _i, in both the same and opposite directions, in different parts of the parathyroid cell.