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 microM 4alpha-phorbol-12,13-didecanoate (4alphaPDD), an agonist of TRPV4. No flow dependence of net K(+) and Na(+) transports or effects of 4alphaPDD on CCDs were observed in TRPV4(-/-) mice. A basolateral application of 4alphaPDD 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.
Taniguchi
Junichi
J
Division of Molecular Pharmacology, Dept. of Pharmacology, Jichi Medical University, Tochigi, Japan.
Tsuruoka
Shuichi
S
Mizuno
Atsuko
A
Sato
Jun-ichi
J
Fujimura
Akio
A
Suzuki
Makoto
M
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000652:urine; D050916:TRPV Cation Channels / Q000172:deficiency / Q000502:physiology*
D010703:Phorbol Esters; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D018999:Charybdotoxin; C008876:phorbol-12,13-didecanoate; D003900:Desoxycorticosterone; D000584:Amiloride; D005665:Furosemide; D011188:Potassium