Upregulation of voltage-dependent outward rectifying K+ (Kv) channels has been reported in activated microglia. Since beta-amyloid peptide (A beta) is known to activate microglia, we tested whether the exposure of cultured rat microglia to A beta fragment 25-35 (A beta 25-35) induced the Kv current. A beta 25-35 in 5-200 nM concentration range significantly increased Kv current density, while there was small change in inward rectifying K+ current density. The full length A beta peptide (A beta 1-42) also increased Kv current. However, the control peptide, A beta 35-25, did not induce Kv current. Most of the Kv current induced by A beta was specifically blocked by the presence of antisense deoxyoligonucleotides against Kv1.3, and Kv1.5. Thus, it is concluded that we have identified Kv1.3 and Kv1.5 as the channel types expressed in A beta-treated microglia.