Functional importance of Ca2+-activated K+ channels for lysophosphatidic acid-induced microglial migration.
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 micro 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 nm charybdotoxin or 10 micro m clotrimazole. In contrast, 5 micro 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 nm charybdotoxin or by 51% during exposure to 10 micro m clotrimazole. Microglial migration was not inhibited by 5 micro m paxilline. It is concluded that IKCa1 Ca(2+)-activated K(+) channels are required for LPA-stimulated migration of microglial cells.
Schilling
Tom
T
Institute of Physiology, Humboldt University Berlin, Tucholsky Strasse 2, D-10117 Berlin, Germany.
Stock
Christian
C
Schwab
Albrecht
A
Eder
Claudia
C
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D018999:Charybdotoxin / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D004347:Drug Interactions; D004553:Electric Conductivity; D004996:Ethidium / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D006131:Growth Inhibitors; D007211:Indoles; D008246:Lysophospholipids; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D018999:Charybdotoxin; C048220:paxilline; D004996:Ethidium; D003022:Clotrimazole; C032881:lysophosphatidic acid