Hypertonicity increases CLC-5 expression in mouse medullary thick ascending limb cells.

Abstract

Genetic studies indicated that mutations of the chloride channel CLC-5 in the kidney are responsible for a group of clinical disorders, collectively called Dent's disease. In the kidney, CLC-5 was found to be expressed in the proximal tubule, medullary thick ascending limb (mTAL) of loop of Henle, and intercalated cells of the collecting tubule. In proximal tubular cells, CLC-5 was found to play an important role in receptor-mediated endocytosis. However, the functional roles of CLC-5 in mTAL and collecting tubules remain unclear. Because mTAL is normally exposed to a hypertonic environment, we aimed to examine the effect of hypertonicity on CLC-5 expression in this nephron segment. Our studies revealed that exposure to hypertonicity (up to 550 mosM) increased CLC-5 mRNA and protein levels in a murine mTAL cell line (MTAL) but not in an opossum kidney (OK) proximal tubular cell line. A similar effect was also found in mouse kidneys, where CLC-5 expression was enhanced in renal medulla, but not cortex, after 48 h of water deprivation. We also tested the effect of hypertonicity on endocytotic activity and found that exposure to hypertonicity caused a significant decrease in cellular uptake of FITC-labeled albumin in OK but not in MTAL cells. Our results suggest that CLC-5 expression is upregulated by hypertonicity in mTAL cells but not in proximal tubular cells. We speculate that the increased CLC-5 levels in mTAL may serve to maintain the endocytotic activity in a hypertonic environment.

• Authors: Phuong-Chi Pham, Olivier Devuyst, Phuong-Thu Pham, Naoko Matsumoto, Remi N G Shih, Oak D Jo, Norimoto Yanagawa, Adam M Sun
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 287 Issue 4 Pg. F747-52 (Oct 2004) ISSN: 1931-857X [Print] United States
• PMID: 15161605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CLC-5 chloride channel
• Chloride Channels
• Hypertonic Solutions
• RNA, Messenger

Topics

• Animals
• Cells, Cultured
• Chloride Channels (genetics, metabolism)
• Endocytosis (physiology)
• Gene Expression
• Hypertonic Solutions (pharmacology)
• Kidney Tubules, Proximal (cytology)
• Loop of Henle (cytology, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Opossums
• RNA, Messenger (metabolism)
• Water Deprivation (physiology)