title: Pressure induces intracellular calcium changes in juxtaglomerular cells in perfused afferent arterioles.
abstract: Calcium (Ca(2+)) has an important role in nearly all types of cellular secretion, with a particularly novel role in the juxtaglomerular (JG) cells in the kidney. In JG cells, Ca(2+) inhibits renin secretion, which is a major regulator of blood pressure and renal hemodynamics. However, whether alterations in afferent arteriolar (Af-Art) pressure change intracellular Ca(2+) concentration ([Ca(2+)](i)) in JG cells and whether [Ca(2+)](i) comes from extracellular or intracellular sources remains unknown. We hypothesize that increases in perfusion pressure in the Af-Art result in elevations in [Ca(2+)](i) in JG cells. We isolated and perfused Af-Art of C57BL6 mice and measured changes in [Ca(2+)](i) in JG cells in response to perfusion pressure changes. The JG cells' [Ca(2+)](i) was 93.3±2.2 nM at 60 mm Hg perfusion pressure and increased to 111.3±13.4, 119.6±7.3, 130.3±2.9 and 140.8±12.1 nM at 80, 100, 120 and 140 mm Hg, respectively. At 120 mm Hg, increases in [Ca(2+)](i) were reduced in mice receiving the following treatments: (1) the mechanosensitive cation channel blocker, gadolinium (94.6±7.5 nM); (2) L-type calcium channel blocker, nifedipine (105.8±7.5 nM); and (3) calcium-free solution plus ethylene glycol tetraacetic acid (96.0±5.8 nM). Meanwhile, the phospholipase C inhibitor, inositol triphosphate receptor inhibitor, T-type calcium channel blocker, N-type calcium channel blocker and Ca(2+)-ATPase inhibitor did not influence changes in [Ca(2+)](i) in JG cells. In summary, JG cell [Ca(2+)](i) rise as perfusion pressure increases; furthermore, the calcium comes from extracellular sources, specifically mechanosensitive cation channels and L-type calcium channels.
authors.affiliation: Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: En Yin
authors.initials: EY
authors.lastname: Lai
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wang
authors.forename: Anders Erik Gosta
authors.initials: AE
authors.lastname: Persson
authors.forename: Roy Davis
authors.initials: RD
authors.lastname: Manning
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D011312:Pressure
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004533:Egtazic Acid; D005682:Gadolinium; D009543:Nifedipine; D002118:Calcium