Differential effects of cell-permeable and cell-impermeable Kv1.3 inhibitors on microglial calcium signaling

Microglia, brain resident immune cells, are a major target for the treatment of many neurodegenerative diseases. However, current approaches that seek to relieve microglia-mediated inflammation are not without adverse effects on beneficial reparative functions. The voltage-gated potassium channel Kv1.3, an effective regulator of membrane potential in T lymphocytes, has been shown to preferentially express in disease-associated human and rodent microglia. Genetic deletion and in vivo treatment with Kv1.3-selective inhibitors prevented inflammation in multiple preclinical rodent models of neurodegenerative diseases.