Cellular Physiology & Biochemistry / A Swelling-Activated Chloride Current in Microglial Cells is Suppressed by Epac and Facilitated by PKA : Impact on Phagocytosis

Background/Aims: Volume-regulated anion channels (VRACs) are of particular importance in regulating the cell volume (CV) and give rise to the swelling-activated Cl- current (ICl,swell), a main component driving global regulatory volume decrease (RVD) during cell swelling. Because ICl,swell affects numerous CV-regulated processes like migration, we assume that its role is also indispensable for phagocytosis which requires local cell swelling. Noradrenaline (NA) modulates phagocytosis in macrophages and microglial cells, macrophage-related cells in the central nervous system. Therefore we evaluated whether NA modulates ICl,swell and phagocytosis in microglia. Methods: Experiments were performed in murine microglial BV-2 and primary mouse microglial cells. Patch clamp experiments were performed in BV-2 cells using the amphotericin-perforated method to minimize cytosolic disturbances. Phagocytosis was quantified by scanning electron microscopy. Results: Following activation of ICl,swell by a hypotonic bath solution, noradrenaline, as well as the -adrenergic agonist isoproterenol, evoked a transient decrease of ICl,swell. Repeated application of adrenergic agonists caused a decline of this electrical response. Application of the agonist of exchange protein directly activated by cAMP (Epac), 8-pCPT-2-O-Me-cAMP, or the protein kinase A inhibitor H89 caused a persistent suppression of ICl,swell. When isoproterenol was added concomitantly with the hypotonic saline, ICl,swell developed more rapidly compared to control conditions. Uptake of IgG-coated beads was suppressed by NA or H89 when quantified after 15 min of exposure. Conclusion: The activation of -adrenergic receptors in microglial cells triggers a cAMP-Epac-dependent and a cAMP-PKA-dependent cascade which affects phagocytosis via modulation of the swelling-activated Cl- current ICl,swell.(VLID)359693

Track Reconstruction with Cosmic Ray Data at the Tracker Integration Facility

The subsystems of the CMS silicon strip tracker were integrated and commissioned at the Tracker Integration Facility (TIF) in the period from November 2006 to July 2007. As part of the commissioning, large samples of cosmic ray data were recorded under various running conditions in the absence of a magnetic field. Cosmic rays detected by scintillation counters were used to trigger the readout of up to 15\,\% of the final silicon strip detector, and over 4.7~million events were recorded. This document describes the cosmic track reconstruction and presents results on the performance of track and hit reconstruction as from dedicated analyses