Effect of flow and stretch on the [Ca 2+ ] i response of principal and intercalated cells in cortical collecting duct

作者：Wen Liu, Shiyun Xu, Craig B. Woda, Paul Kim, Sheldon Weinbaum, Lisa M. Satlin · 发表于：American Journal of Physiology-Renal Physiology · 年份：2003 · DOI：10.1152/ajprenal.00067.2003 · 被引用次数：227 · 研究领域：Genetic and Kidney Cyst Diseases、Cerebrospinal fluid and hydrocephalus、Ion Transport and Channel Regulation

An acute increase in tubular fluid flow rate in the microperfused cortical collecting duct (CCD), associated with a approximately 20% increase in tubular diameter, leads to an increase in intracellular Ca2+ concentration ([Ca2+]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 [Ca2+]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 [Ca2+]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 [Ca2+]i in both principal and intercalated cells within approximately 10 s. This response was mediated by external Ca2+ entry and inositol 1,4,5-trisphosphate-mediated release of cell Ca2+ stores. In split-open CCDs, an increase in superfusate flow led to an approximately twofold increase in [Ca2+]i in both cell types within approximately 30 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...