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 93.32.2 nM at 60 mm Hg perfusion pressure and increased to 111.313.4, 119.67.3, 130.32.9 and 140.812.1 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 (94.67.5 nM); (2) L-type calcium channel blocker, nifedipine (105.87.5 nM); and (3) calcium-free solution plus ethylene glycol tetraacetic acid (96.05.8 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. © 2011 The Japanese Society of Hypertension All rights reserved.