Lysophospholipids induce membrane hyperpolarization in microglia by activation of IKCa1 Ca(2+)-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 microM intracellular free Ca(2+), Ca(2+)-dependent K(+) currents of microglia showed a similar pharmacological profile to lysophospholipid-induced currents. The Ca(2+)-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. Ca(2+) imaging experiments revealed increases in the intracellular free Ca(2+) concentration of microglia to a mean value of about 400 nM after application of 1 microM sphingosine-1-phosphate or 1 microM 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 Ca(2+)-dependent K(+) channels. Increases in the concentration of intracellular free Ca(2+) evoked by the lysophospholipids are sufficient to activate microglial Ca(2+)-dependent K(+) channels.
Schilling
T
T
Institute of Physiology, Humboldt University, Berlin, Germany.
Repp
H
H
Richter
H
H
Koschinski
A
A
Heinemann
U
U
Dreyer
F
F
Eder
C
C
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D008246:Lysophospholipids; D010455:Peptides; D015221:Potassium Channels; D012333:RNA, Messenger; D018999:Charybdotoxin; C060506:sphingosine 1-phosphate; C064719:iberiotoxin; D013110:Sphingosine; D002118:Calcium