Towards the discovery of novel T-type calcium channel blockers

Abstract

Despite their presence in many tissues and their potential implication in various disease states, low-voltage activated T-type calcium channels (T-channels) have only recently become targets of interest. Unfortunately, the lack of selective T-channel blockers has hampered further characterisation of these channels. The recent availability of cloned T-channels, the Ca_V3 proteins, facilitates identification of novel T-channel blockers. Also, studies performed in knockout animals have fostered novel interest. Selective inhibition of T-channels may have clinical importance in cardiovascular diseases, some forms of epilepsy, sleep disorders, pain and possibly cancer. This review focuses on novel research approaches to discover potent and selective T-channel modulators. These molecules may be potential drugs for treating human diseases, as well as important tools to decipher the physiological role of these channels.

Keywords::

• Ca_V3 subunit
• low-voltage activated
• T-type calcium channel

Acknowledgements

The work performed in the laboratory is supported by CNRS, INSERM and grants from Agence Nationale pour la Recherche (ANR N° 06-NEURO-035-01) and Association Française contre les Myopathies (AFM). The authors thank Leigh Anne Swayne and Emmanuel Bourinet for critical reading of the manuscript.