Role of voltage-gated Kv channels in microglial physiology

Microglial activation can exacerbate the neuronal damage seen in various neurodegenerative diseases. K+ channels control the membrane potential in most cells, which may regulate activation; thus, I hypothesize that the activity of specific K+ channels is required for microglial activation. In activated microglia, both Kv1.3 mRNA and protein level increased concomitantly with the upregulation Kv1.3-like current. Similarly, mRNA and protein levels increased for Kv1.2. In contrast, Kv1.5 mRNA and protein levels remained unchanged. In activated microglia, 4-aminopyridine, a Kv1.x channel blocker, eliminated the stimulation-induced increases in respiratory burst and phagocytosis, but not NO production or proliferation. Dendrotoxin treatment, which blocks Kv1.2 and Kv1.6, blocked phagocytosis while agitoxin treatment, which blocks Kv1.3, blocked the respiratory burst. These results imply that alterations in Kv channel expression modulate changes in some of the activation processes in microglia. Taken together, these results suggest that Kv channel blockers are potential targets for inhibiting microglia activation.