Effect of cadmium on gap junctional intercellular communication in primary cultures of rat renal proximal tubular cells

• Published in: Life sciences (1973) 2001-06, Vol.69 (3), p.247-254
• Main Authors: Fukumoto, Masakatsu, Kujiraoka, Toru, Hara, Masayuki, Shibasaki, Toshiaki, Hosoya, Tatsuo, Yoshida, Minoru
• Format: Article
• Language: English
• Subjects: Acetylglucosaminidase - metabolism; Animals; Cadmium; Cadmium Chloride - toxicity; Calcium; Cell Communication - drug effects; Cell Survival - drug effects; Cells, Cultured; Cytotoxicity; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Fluorescent Antibody Technique; Gap junction; Gap Junctions - drug effects; Gap Junctions - ultrastructure; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Kidney Tubules, Proximal - pathology; L-Lactate Dehydrogenase - metabolism; Male; Nitrates - metabolism; Nitric oxide; Primary culture; Proximal tubular cells; Rat; Rats; Rats, Sprague-Dawley; Time Factors
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(01)01063-3

Cadmium mainly accumulates in the kidney and causes renal injury. To clarify the mechanism of Cd nephrotoxicity, we investigated the effects of this element on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Sixty minutes after exposure to 100 μM Cd, dye coupling experiments showed that gap junctional intercellular communication (GJIC) was significantly inhibited. This inhibition occurred before the appearance of cytotoxicity. Intracellular calcium concentrations [Ca 2+] i, which modulate the function of gap junctions, gradually increased after exposure to Cd and reached a maximum after 60 minutes. These results suggest that the inhibition of GJIC as a result of Cd exposure is related to an increase in [Ca 2+] i, and that GJIC inhibition may be an indicator of nephrotoxicity.