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

Abstract

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 µ m 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 Ca 2+ ‐activated K + current. Microglial Ca 2+ ‐activated K + currents were abolished by either 50 n m charybdotoxin or 10 µ m clotrimazole. In contrast, 5 µ m paxilline did not have any significant effects on Ca 2+ ‐activated K + currents. The LPA‐stimulated migration of microglial cells was inhibited by blockers of IKCa1 Ca 2+ ‐activated K + channels. The mean migration rate of LPA‐stimulated cells was decreased by 61% in the presence of 50 n m charybdotoxin or by 51% during exposure to 10 µ m clotrimazole. Microglial migration was not inhibited by 5 µ m paxilline. It is concluded that IKCa1 Ca 2+ ‐activated K + channels are required for LPA‐stimulated migration of microglial cells.