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(V)1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we summarize the recent progress in elucidating the mechanisms involved. Ca(V)1 channels, already advantaged in their responsiveness to depolarization, trigger communication with the nucleus by attracting colocalized clusters of activated CaMKII (Ca(2+)/calmodulin-dependent protein kinase II). Ca(V)2 channels lack this ability, but must work at a distance of >1 μm from the Ca(V)1-CaMKII co-clusters, which hampers their relative efficiency for a given rise in bulk [Ca(2+)](i) (intracellular [Ca(2+)]). Moreover, Ca(2+) influx from Ca(V)2 channels is preferentially buffered by the ER (endoplasmic reticulum) and mitochondria, further attenuating their effectiveness in signalling to the nucleus.