PTH regulates expression of ClC-5 chloride channel in the kidney.
Mutations in the chloride channel, ClC-5, have been described in several inherited diseases that result in the formation of kidney stones. To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1alpha,25(OH)(2) vitamin D(3) with and without thyroparathyroidectomy. Parathyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thyroparathyrodectomized rats had lower serum and higher urinary calcium concentrations compared with control animals as well as lower serum PTH and calcitonin 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, thyroparathyroidectomized rats injected with PTH. No significant changes in ClC-5 mRNA and protein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney cortex and that neither 1alpha,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 lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.
Silva
I V
IV
Eudowood Division of Respiratory Sciences, The Johns Hopkins School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Blaisdell
C J
CJ
Guggino
S E
SE
Guggino
W B
WB
D000818:Animals; D002116:Calcitonin / Q000097:blood; D002118:Calcium / Q000097:blood / Q000652:urine; D018118:Chloride Channels / Q000378:metabolism*; D002762:Cholecalciferol / Q000172:deficiency*; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood*; D016105:Parathyroidectomy; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy; D014808:Vitamin D Deficiency / Q000378:metabolism*
C097503:CLC-5 chloride channel; D018118:Chloride Channels; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D002762:Cholecalciferol; D002116:Calcitonin; D002118:Calcium