Novel Ca receptor signaling pathways for control of renal ion transport

Purpose of review: A rise in extracellular Ca acting through the calcium sensing receptor (CaR) causes physiologically significant loss of Na, K, Cl, Ca, and water. The CaR is expressed in all nephron segments, but its effects on ion and water transport in specific segments as well as the mechanisms by which it regulates ion and water transport is not fully understood. This review will summarize recent information regarding the renal transport effects of the CaR. Recent findings: Considerable progress has been made in characterizing TRPV5, the regulated Ca entry pathway in the distal convoluted tubule (DCT), but precisely how the CaR contributes to its regulation is not known. The CaR interacts with, and inactivates, a K channel, Kir4.1, in the renal distal convoluted tubule. Recently described loss-of-function mutations in this K channel lead to a complicated phenotype that includes salt wasting, suggesting that inactivation of Kir4.1 by the CaR may contribute to the salt wasting observed in response to CaR activation. Summary: The CaR mediates the effects of extracellular Ca on the kidney and is an essential control point in regulation of Ca balance and possibly physiologic regulation of NaCl balance, but the circumstances for regulation of Na balance are not fully established in mammals. The thick ascending limb of Henle and the distal convoluted tubule appear to be the nephron segments most responsible for the effects of the CaR on ion and water transport, although its mechanisms of action are not fully established.