Lead (Pb2+) tends to accumulate in bone from where it is released during bone resorption, thus leading to high local concentrations of Pb2+ with the risk of cellular toxicity. We investigated the interference of Pb2+ with the calcium release activated calcium influx (CRAC) of osteoblast-like (OBL) cells. CRAC was elicited by depletion of intracellular Ca2+ stores with thapsigargin and/or A23187 under Ca2+-free conditions and re-addition of extracellular Ca2+. The fura-2 excitation ratio (R) was used to monitor changes of the free intracellular concentration of Ca2+ and Pb2+, the latter being reversible by the heavy metal chelator TPEN. Five or 12.5 μM Pb2+ applied simultaneously with re-added Ca2+ reduced the immediate CRAC of OBL cells to 70% or 37% of control value, respectively. An enlarged influx of Pb2+ occurred during CRAC, which led to a 2.7-fold faster increase of R. When 1 μM Pb2+ was added during ongoing CRAC, the Pb2+-mediated increase of R correlated with the degree of CRAC (r = 0.83). Inhibitory effects of Pb2+ on Ca2+ ATPase activity did not contribute to the aforementioned findings. Our results demonstrated that CRAC channels of OBL cells are blocked as well as permeated by Pb2+.
- Capacitative calcium current
- Osteoblast-like cells
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine