Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV4

Title: Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron.

Authors: M Mamenko, O Zaika, N Boukelmoune, R G O'Neil, O Pochynyuk

Journal, date & volume: Am. J. Physiol. Renal Physiol., 2015 Feb 15 , 308, F275-86

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25503733

Abstract
Long-standing experimental evidence suggests that epithelial cells in the renal tubule are able to sense osmotic and pressure gradients caused by alterations in ultrafiltrate flow by elevating intracellular Ca(2+) concentration. These responses are viewed as critical regulators of a variety of processes ranging from transport of water and solutes to cellular growth and differentiation. A loss in the ability to sense mechanical stimuli has been implicated in numerous pathologies associated with systemic imbalance of electrolytes and to the development of polycystic kidney disease. The molecular mechanisms conferring mechanosensitive properties to epithelial tubular cells involve activation of transient receptor potential (TRP) channels, such as TRPV4, allowing direct Ca(2+) influx to increase intracellular Ca(2+) concentration. In this review, we critically analyze the current evidence about signaling determinants of TRPV4 activation by luminal flow in the distal nephron and discuss how dysfunction of this mechanism contributes to the progression of polycystic kidney disease. We also review the physiological relevance of TRPV4-based mechanosensitivity in controlling flow-dependent K(+) secretion in the distal renal tubule.