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Both cell volume and calmodulin contribute to the regulation of macula densa nitric oxide
Author(s) -
Komlosi Peter,
Zhang ZhiRen,
Steele Stacy,
Chu WenFeng,
Bell Phillip Darwin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.761.24
Subject(s) - calmodulin , macula densa , chemistry , nitric oxide , nitric oxide synthase , intracellular , calcium , calcium in biology , biophysics , endocrinology , microbiology and biotechnology , medicine , biochemistry , biology , renin–angiotensin system , organic chemistry , blood pressure
Elevations in luminal sodium chloride concentration ([NaCl] L ) alter macula densa (MD) intracellular calcium concentration and result in the release of nitric oxide (NO). Also, concomitant elevations in [NaCl] L and luminal osmolality (osm L ) lead to shrinkage of macula densa cells, while increases in [NaCl] L at constant osm L produce cell swelling. Currently, there is little information concerning the intracellular signaling event that leads to the activation of MD NO synthase. Current studies were performed to determine whether changes in MD cell volume and/or calmodulin‐dependent signaling activate MD NO synthase. Thick ascending limb‐glomerulus preparations were isolated and perfused from rabbits, and MD NO release was detected with fluorescence microscopy using DAF‐FM. Elevations in [NaCl] L (from 0 to 150 mmol/L) at constant osm L produced an increase in DAF‐FM fluorescence of 5±0.5%, while concomitant elevations in [NaCl] L and osm L led to an increase of 12±0.7%. Luminal application of furosemide, a blocker of Na + :2Cl ‐ :K + cotransport, reversed [NaCl] L ‐dependent NO release (‐0.04±0.2%). Also, application of the calmodulin‐inhibitor calmidazolium blocked [NaCl] L ‐dependent NO release (1.8±1.8%). Thus, [NaCl] L ‐dependent NO production by MD cells may be modulated by changes in cell volume and requires activation of calmodulin signaling.