Chemokine modulation of high-conductance Ca(2+)-sensitive K(+) currents in microglia from human hippocampi.
During acute pathological processes, microglia transform into an activated state characterized by a defined morphology and current profile, and are recruited to injury sites by chemokines. No information is available on the ion channels and the mode of action of chemokines in microglia in brain slices from humans with a chronic pathology. Thus, patch-clamp recordings of microglia were performed in hippocampal slices from seven patients who underwent surgery for pharmaco-resistant epilepsy. Cells were identified as microglia by positive labelling with fluorescein-conjugated tomato lectin before recording. All the recorded cells had an ameboid morphology characteristic of activated microglia. However, they had a high input resistance (3.6 G omega), a zero-current resting potential of -16 mV, and lacked Na+ currents, inwardly rectifying and delayed rectifying K+ currents such as non-activated microglia. Importantly, recorded cells expressed Ca2+-sensitive outward currents that activated at 0 mV with non-buffered intracellular Ca2+ and were sensitive to 1 mm tetraethylammonium (TEA). The estimated single-channel conductances were 187 pS in cell-attached and 149 pS in outside-out patches, similar to those of high-conductance Ca2+-dependent K+ channels. The chemokine MIP1-alpha increased whole-cell outward current amplitudes measured at +60 mV by a factor of 3.3. Thus, microglia in hippocampi from epileptic patients express high-conductance Ca2+-dependent K+ channels that are modulated by the chemokine MIP1-alpha. This modulation may contribute to the migratory effect of MIP1-alpha on microglia.
Bordey
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Department of Neurosurgery, Cellular and Molecular Physiology, Yale University, 333 Cedar Street, LSOG 228, New Haven, CT 06520-8082, USA. angelique.bordey@yale.edu
Spencer
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D002118:Calcium / Q000502:physiology*; D054407:Chemokine CCL4; D018925:Chemokines / Q000494:pharmacology*; D004553:Electric Conductivity; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D017628:Microglia / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D037121:Plant Lectins / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D037121:Plant Lectins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C034981:tomato lectin; D019789:Tetraethylammonium; D002118:Calcium