Details

Autor(en) / Beteiligte

• Berrout, Jonathan
• Jin, Min
• Mamenko, Mykola
• Zaika, Oleg
• Pochynyuk, Oleh
• O'Neil, Roger G.

Titel

Function of Transient Receptor Potential Cation Channel Subfamily V Member 4 (TRPV4) as a Mechanical Transducer in Flow-sensitive Segments of Renal Collecting Duct System

Ist Teil von

• The Journal of biological chemistry, 2012-03, Vol.287 (12), p.8782-8791

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• The TRPV4 Ca2+-permeable channel is sensitive to mechanical stimuli. In the current study we have employed immunocytochemical staining in kidney slices and functional assessments (Ca2+ imaging) in isolated, split-opened, tubule segments to define TRPV4 sites of expression and flow-dependent function in the collecting duct system. Staining patterns revealed strong expression of TRPV4 along the entire collecting duct system with highest levels at the apical (luminal)/subapical region of the principal cells (PCs), the dominant cell type, with more diffuse staining in intercalated cells (ICs). Using fluorescence Ca2+ imaging and the selective TRPV4 agonist, GSK1016790A, we demonstrated functional TRPV4 channels in PCs and ICs of split-opened cortical collecting ducts and connecting tubules. The agonist was ineffective in inducing a rise in [Ca2+]i in the absence of extracellular Ca2+ or in tubules from TRPV4-deficient animals. Most importantly, a 10-fold elevation in luminal (apical) fluid flow induced a rapid and sustained influx of Ca2+ that was abolished by the TRPV channel inhibitor, ruthenium red, or in tubules isolated from TRPV4 deficient animals. We concluded that TRPV4 is highly expressed along the entire collecting duct system where it appears to function as a sensor/transducer of flow-induce mechanical stresses. TRPV4 is a Ca2+-permeable channel that is expressed in a wide range of cells and tissues. TRPV4 is expressed in renal connecting tubule/collecting duct cells and is activated by fluid flow. TRPV4 is critical as a flow transducer in the mammalian collecting duct system. TRV4 may underlie mechanically sensitive phenomena in the distal nephron.