Lysophospholipids induce membrane hyperpolarization in microglia by activation of IKCa1 Ca2+-dependent K+ channels

Effects of the lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid were studied in cultured murine microglia using the patch-clamp and video imaging techniques. Both lysophospholipids induced transient membrane hyperpolarization and K+ current activation. The lysophospholipid-induced K+ current was blocked by charybdotoxin or iberiotoxin, but was unaffected by apamin. In recordings with 1 μM intracellular free Ca2+, Ca2+-dependent K+ currents of microglia showed a similar pharmacological profile to lysophospholipid-induced currents. The Ca2+-dependent K+ channels activated in microglia by lysophospholipids are most likely encoded by the IKCa1 channel gene. The presence of IKCa1 mRNA in microglia was demonstrated by reverse transcriptase-polymerase chain reaction studies. Ca2+ imaging experiments revealed increases in the intracellular free Ca2+ concentration of microglia to a mean value of about 400 nM after application of 1 μM sphingosine-1-phosphate or 1 μM lysophosphatidic acid.We suggest that the transient membrane hyperpolarization seen in microglia following exposure to sphingosine-1-phosphate or lysophosphatidic acid is caused by activation of IKCa1 Ca2+-dependent K+ channels. Increases in the concentration of intracellular free Ca2+ evoked by the lysophospholipids are sufficient to activate microglial Ca2+-dependent K+ channels. [Copyright &y& Elsevier]