Location isn't everything

Elevations in the intracellular concentration of Ca²⁺ can lead to the activation of transcription, and Ca²⁺ entry through L-type voltage-gated channels seems to be particularly effective in this regard. So far, this effectiveness has been explained in terms of the spatial coupling of these channels to the signalling pathways that link Ca²⁺ entry with transcription, but now Liu et al. challenge such a view by showing that location might not be the whole story. They report that the magnitude of the Ca²⁺ elevations through L-type channels is much larger than through other types when the increases are elicited by synaptic-like stimuli.

The authors expressed different types of recombinant Ca²⁺ channel on HEK 293 cells and examined their responses to voltage waveforms that mimicked gamma and theta bursts — forms of neuronal activity that are found in vivo. They observed that, at physiological temperatures, Ca²⁺ elevations mediated by L-type channels were about three times larger than the increases mediated by P/Q- and N-type channels. This effect could be explained by the stimulus-dependent inactivation of these two types of channel.

So, in addition to spatial coupling, the characteristics of synaptic activity might be important to determine the relevance of L-type channels to transcriptional activation. A crucial step to establish the true physiological significance of this mechanism will be to investigate whether Ca²⁺ channels in native neurons also show these differences in function.