Modulation of luminal L-alanine transport in proximal tubular cells of frog kidney induced by low micromolar Cd2+ concentration

Abstract

The kidneys are recognized as a major target of cadmium-induced toxicity. However, all mechanisms that are involved in the early stages of cadmium nephrotoxicity, particularly considering low micromolar concentrations of cadmium ions (Cd²⁺) are still unknown. Therefore, the aim of this study was to investigate the effects of peritubular acute exposure to micromolar Cd²⁺ concentration (2.3 μmol/L) on the rapid depolarization and the rate of slow repolarization of peritubular membrane potential difference (PD), induced by luminal application of L-alanine in proximal tubular cells of frog kidney. The results showed that the luminal application of L-alanine rapidly depolarized the peritubular membrane PD of -42.00 ± 11.68 mV by 23.89 ± 4.15 mV with an average rate of slow repolarization of 5.64 ± 0.81 mV/min. Additionally, peritubular acute exposure to Cd²⁺ induced change in rapid depolarization of peritubular membrane PD of -53.33 ± 13.01 mV by 18.78 ± 3.31 mV (P < 0.01) after luminal application of L-alanine. Also, peritubular acute exposure to Cd²⁺ led to statistically significant decrease in the rate of slow repolarization of peritubular membrane PD (3.53 ± 0.35 mV/min; P < 0.05). In conclusion, these results suggest that peritubular acute exposure to low micromolar Cd²⁺ concentration decreased the rapid depolarization and the rate of slow repolarization of peritubular membrane PD induced by luminal application of L-alanine. This is followed by reduced luminal sodium-coupled transport of L-alanine and this change may be one of the possible mechanisms involved in the early stages of Cd²⁺-induced nephrotoxicity.

Keywords: Cadmium; Membrane potential; Nephrotoxicity; Proximal tubule cell; Sodium-coupled transport.