Chronic hyperglycemia and in-vivo Ang II treatment, a model of hypertension, activate CaV1.2 channel-mediated Ca2+ sparklets and calcineurin (CaN). AKAP150 anchors activated CaN to dephosphorylate and activate NFATc3. Subsequently, nuclear translocation of activated NFATc3 leads to reduced transcription of KV2.1, which decreases KV current density. Green and red arrows indicate activation and inhibition, respectively.