The mechanism underlying a hypercholinergic state in Parkinson's disease (PD) remains uncertain. Here, we show that disruption of the K_v1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that K_v1 channels containing K_v1.3 subunits contribute significantly to the orphan potassium current known as I_sAHP in striatal cholinergic interneurons. Typically, this K_v1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by K_v1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting K_v1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of K_v1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on K_Ca channels.