TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct

The transient receptor vanilloid-4 (TRPV4) is a mechanosensitive, swell-activated cation channel that is abundant in the renal distal tubules. Immunolocalization studies, however, present conflicting data as to whether TRPV4 is expressed along the apical and/or basolateral membranes. To disclose the role of TRPV4 in flow-dependent K+ secretion in distal tubules in vivo, urinary K+ excretion and net transports of K+ and Na+ in the cortical collecting duct (CCD) were measured with an in vitro microperfusion technique in TRPV4(+/+) and TRPV4(-/-) mice. Both net K+ secretion and Na+ reabsorption were flow dependently increased in the CCDs isolated from TRPV4(+/+) mice, which were significantly enhanced by a luminal application of 50 mu M 4 alpha-phorbol-12,13-didecanoate (4 alpha PDD), an agonist of TRPV4. No flow dependence of net K+ and Na+ transports or effects of 4 alpha PDD on CCDs were observed in TRPV4(+/+) mice. A basolateral application of 4 alpha PDD had little effect on these ion transports in the TRPV4(+/+) CCDs, while the luminal application did. Urinary K+ excretion was significantly smaller in TRPV4(-/-) than in TRPV4(-/-) mice when urine production was stimulated by a venous application of furosemide. These observations suggested an essential role of the TRPV4 channels in the luminal or basolateral membrane as flow sensors in the mechanism underlying the flow-dependent K+ secretion in mouse CCDs.