β-amyloid peptide induces the expression of voltage dependent outward rectifying K+ channels in rat microglia

Physiology of Microglia

“…Interestingly, the embryonic microglia treated with pneumococcal cell walls despite showing all signs of activation (such as morphological shift, release of TNF-␣, and downregulation of IK IR ) did not demonstrate an upregulation of IK DR (226), suggesting a developmental remodeling of an ion channel-related activation program (226). ␤-Amyloid pro-tein fragment 25-45 (A␤ ) as well as with full-length ␤-amyloid peptide (A␤ ) triggered the upregulation of K v 1.3 and K v 1.5 channels in cultured rat microglial cells (161). The amplitudes of IK DR (similar in their parameters to K v 1.3-generated currents) were ϳ5.6 times larger in activated microglial cells from organotypically cultured (5-7 days) hippocampal slices compared with resting microglia in acutely prepared slices (802).…”

Regulating Factors for Microglial Activation.

“…23,24) Various protein kinases affect each other, that is, "cross talk" of intracellular signaling occurs. 25) reported that the fragment Ab [25][26][27][28][29][30][31][32][33][34][35] triggers the release of NO and TNFa from cultured microglia. Ab-stimulated microglia also release IL-1b.…”

“…26,27) Ab peptides stimulate the production of O 2 Ϫ and the production is inhibited by inhibitors of tyrosine kinases or phosphatidylinositol 3-kinase and by dibutyryl cAMP (dbcAMP), and is potentiated by IFNg or TNFa. 28) Ab peptides have other activity in addition to microglial activation, such as inducing the outward rectifying K channel 29) and elevating intracellular Ca 2ϩ level. 30) Furthermore, Ab peptide 31) and soluble amyloid precursor protein (sAPP) 32) enhance glutamate release by cystine exchange as a consequence of autoprotective antioxidant glutathione production within the microglia, ultimately causing synaptic degeneration and neuronal death.…”

“…131) A neuroprotective role of microglia is suggested by the finding that GLT-1 is highly expressed in activated microglia following facial nerve axotomy. 132) After treatment with Ab peptide [25][26][27][28][29][30][31][32][33][34][35], an increase in both reverse and forward glutamate transport is observed in cultured microglia using electrophysiologic techniques, suggesting a possible cause of neuronal damage. 31) 6.…”

Association of Kv1.5 and Kv1.3 Contributes to the Major Voltage-dependent K+ Channel in Macrophages

“…9 and 10 and references herein) are significantly different from those described in macrophages (8,10,11). In addition, unlike T-lymphocytes, brain and bone marrow macrophages also express Kv1.5 (8,10,(11)(12)(13)(14)(15). Kv1.3 and Kv1.5 differ in their biophysical and pharmacological properties and show distinct regulation in a number of cell types (8, 16 -18).…”