Extracellular Ca2+ directly regulates tight junctional permeability in the human cervical cell line CaSki

Abstract

Lowering extracellular calcium concentration ([Ca2+]o) increases acutely and reversibly the transepithelial electrical conductance (G(TE)) and the epithelial permeability to pyranine (Ppyr) across CaSki cultures. Effects were already observed after lowering calcium from 1.2 to 1.0 mM and were maximal at 0.1 mM. The dose-response curves were sigmoidal (calcium concentration that produces half-maximal effect = 0.3 mM), and the time courses indicated simple exponential trends (time constants of 4-5 min). The effect of calcium was not mediated by mobilization of cytosolic calcium or altering calcium influx, and manganese was found to be a partial agonist to [Ca2+]o. The effects of [Ca2+]o, on permeability were additive to those of hypertonic conditions, indicating that calcium modulates junctional permeability. The experimental data were fitted to theoretical models that relate changes in G(TE) to the probability of assembled/disassembled tight junctions. The results suggest that calcium interacts directly and cooperatively at extracellular sites with junctional elements that are arranged in parallel, and it shifts the probability state of the junctions from "open" to "closed" state. Changes in extracellular calcium may affect the permeability of tight junctions of the cervical epithelium and may play a role in regulating production of cervical mucus.