Mutations in the CACNA1A gene are associated with neurological disorders, such as ataxia, hemiplegic migraine, and epilepsy. These mutations affect the pore-forming α_1A-subunit of Ca_V2.1 channels and thereby either decrease or increase neuronal Ca²⁺ influx. A decreased Ca_V2.1-mediated Ca²⁺ influx has been shown to reduce the regularity of cerebellar Purkinje cell activity and to induce episodic cerebellar ataxia. However, little is known about how ataxia can be caused by CACNA1A mutations that increase the Ca²⁺ influx, such as the S218L missense mutation. Here, we demonstrate that the S218L mutation causes a negative shift of voltage dependence of Ca_V2.1 channels of mouse Purkinje cells and results in lowered thresholds for somatic action potentials and dendritic Ca²⁺ spikes and in disrupted firing patterns. The hyperexcitability of Cacna1a^S218L Purkinje cells was counteracted by application of the activators of Ca²⁺-dependent K⁺ channels, 1-EBIO and chlorzoxazone (CHZ). Moreover, 1-EBIO also alleviated the irregularity of Purkinje cell firing both in vitro and in vivo, while CHZ improved the irregularity of Purkinje cell firing in vitro as well as the motor performance of Cacna1a^S218L mutant mice. The current data suggest that abnormalities in Purkinje cell firing contributes to cerebellar ataxia induced by the S218L mutation and they advocate a general therapeutic approach in that targeting Ca²⁺-dependent K⁺ channels may be beneficial for treating ataxia not only in patients suffering from a decreased Ca²⁺ influx, but also in those suffering from an increased Ca²⁺ influx in their Purkinje cells.