BackgroundThe differential adaptations of cerebrovasculature and small mesenteric arteries could be one of critical factors in postspaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. We hypothesize that there is a differential regulation of intracellular Ca2+ determined by the alterations in the functions of plasma membrane CaL channels and ryanodine-sensitive Ca2+ releases from sarcoplasmic reticulum (SR) in cerebral and small mesenteric vascular smooth muscle cells (VSMCs) of simulated microgravity rats, respectively.Methodology/Principal FindingsSprague-Dawley rats were subjected to 28-day hindlimb unweighting to simulate microgravity. In addition, tail-suspended rats were submitted to a recovery period of 3 or 7 days after removal of suspension. The function of CaL channels was evaluated by patch clamp and Western blotting. The function of ryanodine-sensitive Ca2+ releases in response to caffeine were assessed by a laser confocal microscope. Our results indicated that simulated microgravity increased the functions of CaL channels and ryanodine-sensitive Ca2+ releases in cerebral VSMCs, whereas, simulated microgravity decreased the functions of CaL channels and ryanodine-sensitive Ca2+ releases in small mesenteric VSMCs. In addition, 3- or 7-day recovery after removal of suspension could restore the functions of CaL channels and ryanodine-sensitive Ca2+ releases to their control levels in cerebral and small mesenteric VSMCs, respectively.ConclusionsThe differential regulation of CaL channels and ryanodine-sensitive Ca2+ releases in cerebral and small mesenteric VSMCs may be responsible for the differential regulation of intracellular Ca2+, which leads to the altered autoregulation of cerebral vasculature and the inability to adequately elevate peripheral vascular resistance in postspaceflight orthostatic intolerance.

As label-free biomarkers, biophysical properties of cells are widely used for cell type classification. However, intrinsic biophysical markers, e.g., specific membrane capacitance (C specific membrane ), cytoplasm conductivity (σ conductivity ) and instantaneous Young's modulus (E instantaneous ) measured for hundreds of single cells were not yet reported. In this study, single cells in suspension (adherent cells treated with trypsin) were aspirated through a microfluidic constriction channel at 25°C, and the entry processes and impedance profiles were recorded and translated to C specific membrane , σ conductivity and E instantaneous . C specific membrane , σ conductivity and E instantaneous of five cell types were quantified as 2.10 ± 0.38 μF cm − 2 , 0.91 ± 0.15 S m − 1 and 5.52 ± 0.95 kPa for H460 cells (n cell = 437); 2.52 ± 0.54 μF cm − 2 , 0.83 ± 0.12 S m − 1 and 5.54 ± 1.04 kPa for H446 cells (n cell = 410); 2.45 ± 0.57 μF cm − 2 , 0.99 ± 0.18 S m − 1 and 5.16 ± 1.68 kPa for A549 cells (n cell = 442); 1.86 ± 0.31 μF cm − 2 , 1.07 ± 0.18 S m − 1 and 3.86 ± 0.81 kPa for 95D cells (n cell = 415); 2.03 ± 0.35 μF cm − 2 , 0.99 ± 0.16 S m − 1 and 3.49 ± 0.70 kPa for 95C cells (n cell = 290). The database of C specific membrane , σ conductivity and E instantaneous may serve as a reference for future studies of cellular biophysical properties.