The alpha subunit of the L-type calcium channel (Ca_V1.2) is encoded by the gene CACNA1C. An apparently obscure protein, Ca_V1.2 has risen to prominence in the last five years.

Several large scale genome-wide association (GWAS) studies are in agreement that variation in CACNA1C is associated with bipolar disorder and schizophrenia. Additionally, mutations in CACNA1C are a direct cause of autism. As a consequence, Ca²⁺ signalling has begun to receive attention amongst psychiatrists.

A recent review by Michael Berridge is the ideal introduction to Ca²⁺ dynamics. Calcium does not only enter cells via channels. There are intracellular stores, which can be stimulated to release Ca²⁺ into the cytosol. Neurotransmitters such as serotonin, noradrenaline and glutamate can invoke the release of Ca²⁺  from intracellular stores by way of an intermediate 2nd messenger pathway, the phosphatidylinositol 4,5 biphosphate (PIP2) system. Berridge is best known for having deciphered the foundations of the PIP2 system in the 1980’s and as such he is an authoratative guide for the relevance of calcium signalling to psychiatric disorders.

The full paper is available here.