Functional importance of Ca2+-activated K+ channels for lysophosphatidic acid-induced microglial migration

Authors

  • Tom Schilling,

    1. Institute of Physiology, Humboldt University Berlin, Tucholsky Strasse 2, D-10117 Berlin, Germany
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  • Christian Stock,

    1. Institute of Physiology, University of Wuerzburg, Roentgenring, Wuerzburg, Germany
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    • *

      Present address: Institute of Physiology II, University of Muenster, Robert-Koch Strasse 27a, D-48149 Muenster, Germany

  • Albrecht Schwab,

    1. Institute of Physiology, University of Wuerzburg, Roentgenring, Wuerzburg, Germany
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      Present address: Institute of Physiology II, University of Muenster, Robert-Koch Strasse 27a, D-48149 Muenster, Germany

  • Claudia Eder

    1. Institute of Physiology, Humboldt University Berlin, Tucholsky Strasse 2, D-10117 Berlin, Germany
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: Dr Claudia Eder, as above.
E-mail: claudia.eder@charite.de

Abstract

Migration of microglial cells towards damaged tissue plays a key role in central nervous system regeneration under pathological conditions. Using time lapse video microscopy we show that lysophosphatidic acid (LPA) enhances chemokinetic migration of murine microglial cells. In the presence of 1 µm LPA, the mean migration rate of microglial cells was increased 3.8-fold. In patch-clamp studies we demonstrate that LPA induces activation of a Ca2+-activated K+ current. Microglial Ca2+-activated K+ currents were abolished by either 50 nm charybdotoxin or 10 µm clotrimazole. In contrast, 5 µm paxilline did not have any significant effects on Ca2+-activated K+ currents. The LPA-stimulated migration of microglial cells was inhibited by blockers of IKCa1 Ca2+-activated K+ channels. The mean migration rate of LPA-stimulated cells was decreased by 61% in the presence of 50 nm charybdotoxin or by 51% during exposure to 10 µm clotrimazole. Microglial migration was not inhibited by 5 µm paxilline. It is concluded that IKCa1 Ca2+-activated K+ channels are required for LPA-stimulated migration of microglial cells.

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