PTH regulates expression of ClC-5 chloride channel in the kidney

Mutations in the chloride channel, ClC-5, have been described in several in herited diseases that result in the formation of kidney stones. To determin e whether ClC-5 is also involved in calcium homeostasis, we investigated wh ether ClC-5 mRNA and protein expression are modulated in rats deficient in 1 alpha,25(OH)(2) vitamin DQ With and without thyroparathyroidectomy. Parat hyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thy roparathyrodectomized rate had lower serum and higher urinary calcium conce ntrations compared with control animals as well as lower serum PTH and calc itonin concentrations. ClC-5 mRNA and protein levels in the cortex decrease in vitamin D-deficient, thyroparathyroidectomized rats compared with both control and vitamin D-deficient animals. ClC-5 mRNA and protein expression increase near to control levels in vitamin D-deficient, thyroparathyroidect omized rats injected with PTH. No significant changes in ClC-5 mRNA and pro tein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney c ortex and that neither 1 alpha,25(OH)(2) vitamin D-3 nor PTH regulates ClC- 5 expression in the medulla. The pattern of expression of ClC-5 varies with urinary calcium. Animals with higher urinary calcium concentrations have l ower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.