Maitotoxin stimulates Cd influx in Madin-Darby kidney cells by activating Ca-permeable cation channels

This study examined the role of calcium channels for the uptake of cadmium (Cd) into Madin-Darby canine kidney (MDCK) cells. Maitotoxin, an activator of different types of calcium channels, increased accumulation of ¹⁰⁹Cd and ⁴⁵Ca in MDCK cells. We found that maitotoxin increased accumulation by stimulating ¹⁰⁹Cd influx because it did not affect efflux. An inhibitor of store-operated Ca channels, SKF96365, partially blocked ⁴⁵Ca influx but did not affect ¹⁰⁹Cd influx. Ni and Mn, and loperamide and proadifen (SKF 525a), inhibited ⁴⁵Ca and ¹⁰⁹Cd influx in cells stimulated with maitotoxin, but La and nifedipine did not. Overnight treatment with phorbol 12, 13-ibutyrate (PDBu) to activate protein kinase C resulted in a decrease in the concentration of maitotoxin needed to stimulate ⁴⁵Ca and ¹⁰⁹Cd influx. The effect of PDBu was blocked by treating cells with the protein kinase C inhibitor GF109203X. Additionally, the effect of PDBu was lost in cells treated with an inhibitor of RNA synthesis actinomycin D. These results suggest that a Ca permeable cation channel different from voltage-dependent and store-operated Ca channels mediates the uptake of Cd in MDCK cells. The expression of this channel is regulated by protein kinase C. (C) 2000 Harcourt Publishers Ltd.