Exploring the dominant role of Cav1 channels in signalling to the nucleus

Calcium is important in controlling nuclear gene expression through the activation of multiple signal-transduction pathways in neurons. Compared with other voltage-gated calcium channels, Ca_V1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we summarize the recent progress in elucidating the mechanisms involved. Ca_V1 channels, already advantaged in their responsiveness to depolarization, trigger communication with the nucleus by attracting colocalized clusters of activated CaMKII (Ca²⁺/calmodulin-dependent protein kinase II). Ca_V2 channels lack this ability, but must work at a distance of >1 μm from the Ca_V1-CaMKII co-clusters, which hampers their relative efficiency for a given rise in bulk [Ca²⁺]_i (intracellular [Ca²⁺]). Moreover, Ca²⁺ influx from Ca_V2 channels is preferentially buffered by the ER (endoplasmic reticulum) and mitochondria, further attenuating their effectiveness in signalling to the nucleus.