Targeting voltage-gated calcium channels in neurological and psychiatric diseases

Key Points Voltage-gated calcium channels are of critical importance for nervous system function at the cellular and network levels. Aberrant calcium channel function is associated with a wide range of neurological and psychiatric conditions. Calcium channel dysfunction can occur as a result of mutations in genes encoding calcium channels, or owing to alterations in channel trafficking and regulation. Calcium channel blockers may be effective in the treatment of Parkinson disease, drug addiction, pain, anxiety and epilepsy. Cell-specific alternative splicing of calcium channel genes creates additional calcium channel diversity and is an important consideration in drug design. The development of new calcium channel inhibitors is challenging, and may require unconventional approaches such as targeting associations with interacting proteins. Dysfunction of voltage-gated calcium channels is associated with a variety of neurological and psychiatric conditions. Several drugs that block these channels are already in clinical use, with new agents currently in development. Here, Zamponi highlights the functions of voltage-gated calcium channels and assesses their potential as therapeutic targets for nervous system disorders. Voltage-gated calcium channels are important regulators of brain, heart and muscle functions, and their dysfunction can give rise to pathophysiological conditions ranging from cardiovascular disorders to neurological and psychiatric conditions such as epilepsy, pain and autism. In the nervous system, calcium channel blockers have been used successfully to treat absence seizures, and are emerging as potential therapeutic avenues for pathologies such as pain, Parkinson disease, addiction and anxiety. This Review provides an overview of calcium channels as drug targets for nervous system disorders, and discusses potential challenges and opportunities for the development of new clinically effective calcium channel inhibitors.