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.
Olivi
L
L
Division of Toxicology, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Bressler
J
J
D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002106:Cadmium Radioisotopes / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002132:Calcium Radioisotopes / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008139:Loperamide / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D035964:Oxocins; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D000095702:Polyether Toxins
D002104:Cadmium; D002106:Cadmium Radioisotopes; D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D007093:Imidazoles; D007473:Ion Channels; D008139:Loperamide; D008387:Marine Toxins; D009543:Nifedipine; D035964:Oxocins; D011493:Protein Kinase C; D012313:RNA; C020394:maitotoxin; D000095702:Polyether Toxins; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole