Renal TRPathies.
Many ion channels and transporters are involved in the filtration, secretion, and resorption of electrolytes by the kidney. In recent years, the superfamily of transient receptor potential (TRP) ion channels have received deserved attention because mutated TRP channels are linked to human kidney diseases. This review focuses on two TRP members--TRPC6 and TRPM6--and their functions in the kidney. Gain-of-function mutations in TRPC6 are the cause for progressive kidney failure with urinary protein loss such as FSGS. Thus, TRPC6 is an essential signaling component in a functional slit diaphragm formed by podocytes around the glomerular capillaries. Loss-of-function mutations in TRPM6 are a molecular cause of hypomagnesemia with secondary hypocalcemia, suggesting that TRPM6 is critically involved in transcellular Mg2+ transport in the kidney. Here, we highlight how recent studies analyzing function and expression of these channels in the kidney improve our mechanistic understanding of TRP channel function in general and pave the way to new, promising therapeutic strategies to target kidney diseases such as FSGS and hypomagnesemia with secondary hypocalcemia.
Dietrich
Alexander
A
Institute of Pharmacology and Toxicology, School of Medicine, University of Marburg, Marburg, Germany.
Chubanov
Vladimir
V
Gudermann
Thomas
T
D006706:Homeostasis; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008274:Magnesium / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics*; D000074287:TRPC6 Cation Channel; D050053:TRPM Cation Channels / Q000235:genetics*
D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D008274:Magnesium