Aldosterone and high-NaCl diet modulate ClC-2 chloride channel gene expression in rat kidney

It is well known that Na⁺ reabsorption in the kidney can be regulated by aldosterone. Although Cl^- is the most abundant anion present in the extra cellular fluids the involvement of aldosterone in the regulation of Cl^- conductance through Cl^- channels at the molecular level is unknown. In this study, the effects of aldosterone and high-Na⁺ diet on the expression of ClC-2, a cell volume-, pH- and voltage-sensitive Cl^- channel, was examined in the rat kidney. Total RNA isolated from Wistar rats fed a high-Na⁺ diet for 5 days, furosemide treatment, adrenalectomy and adrenalectomy with replacement of normal plasma levels of aldosterone were compared by the use of ribonuclease protection assay (RPA), and/or a semi-quantitative RT-PCR. The high-Na⁺ diet reduced renal mRNA and protein ClC-2 expression. The renal expression of ClC-2 mRNA decreased in adrenalectomized rats and was restored by plasma aldosterone replacement. In addition, the semi-quantitative RT-PCR in different segments of the nephron showed that these changes were secondary to the modulation of ClC-2 mRNA expression by aldosterone in the cortical and medullary segments of thick ascending limbs of Henle's loop. These results suggest that ClC-2 may be involved with aldosterone-induced Cl^- transport in the kidney.