期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 285, 期 5, 页码 F998-F1012出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00067.2003
关键词
cilium; cytoskeletal deformation; fluid shear stress; mechanotransduction; fura 2; intracellular calcium concentration
资金
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [T32HD007537] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR009145] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R37DK051391, R01DK038470, R01DK064104, R29DK038470, R01DK051391] Funding Source: NIH RePORTER
- NCRR NIH HHS [1 S10 RR0 9145-01] Funding Source: Medline
- NICHD NIH HHS [T32 HD-07537] Funding Source: Medline
- NIDDK NIH HHS [DK-64104, DK-38470, DK-51391] Funding Source: Medline
An acute increase in tubular fluid flow rate in the microperfused cortical collecting duct (CCD), associated with a similar to20% increase in tubular diameter, leads to an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in both principal and intercalated cells (Woda CB, Leite M Jr, Rohatgi R, and Satlin LM. Am J Physiol Renal Physiol 283: F437-F446, 2002). The apical cilium present in principal but not intercalated cells has been proposed to be a flow sensor. To determine whether flow across the cilium and/or epithelial stretch mediates the [Ca(2+)](i) response, CCDs from New Zealand White rabbits were microperfused in vitro, split-open (to isolate the effect of flow across cilia), or occluded ( to examine the effect of stretch and duration/magnitude of the flow impulse), and [Ca(2+)](i) was measured using fura 2. In perfused and occluded CCDs, a rapid (<1 s) but not slow (>3 min) increase in luminal flow rate and/or circumferential stretch led to an approximately threefold increase in [Ca(2+)](i) in both principal and intercalated cells within similar to10 s. This response was mediated by external Ca(2+) entry and inositol 1,4,5-trisphosphate-mediated release of cell Ca(2+) stores. In split-open CCDs, an increase in superfusate flow led to an approximately twofold increase in [Ca(2+)](i) in both cell types within similar to30 s. These experimental findings are interpreted using mathematical models to predict the fluid stress on the apical membranes of the CCD and the forces and torques on and deformation of the cilia. We conclude that rapid increases in luminal flow rate and circumferential stretch, leading to shear or hydrodynamic impulses at the cilium or apical membrane, lead to increases in [Ca(2+)](i) in both principal and intercalated cells.
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