TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs.

CABRAL PABLO; CAPURRO CLAUDIA; GARVIN JEFFREY

ACTA PHYSIOLOGICA

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015 vol. 214 p. 319 - 328

1748-1708

Medullary thick ascending limbs (mTAL) regulate Na balance and therefore blood pressure. We previously showed that cell swelling activates the mechano-sensitive channel TRPV4 in this segment. This Ca permeable channel can also be activated by luminal flow in other cell types. Aim: we hypothesized that TRPV4 mediates flow-induced increases in intracellular Ca (Cai) in rat mTALs. Methods: We performed ratiometric measurements of Cai in perfused mTALs. Results: Increasing luminal flow from 0 to 20 nL min-1 caused Cai to peak 231±29 nmol L-1 above basal concentrations (n=18). The general TRPV inhibitor ruthenium red at 15 and 50 umol L-1 reduced peak Cai by 41±9 (p