Excitation-Transcription Coupling: Signaling by Ion Channels to the Nucleus

Changes in the concentration of intracellular Ca 2+ (Ca 2+ i ) in response to various stimuli play a role in regulating numerous cellular processes, including the activation of gene expression. In neurons, the extraordinary diversity of the response to Ca 2+ signaling depends on the location, intensity, and duration of the Ca 2+ transient. Interestingly, Ca 2+ -dependent gene transcription appears to be sensitive both to increases in nuclear Ca 2+ , which occur after relatively intense stimuli, and to highly localized increases in Ca 2+ near the sites of Ca 2+ influx. Activation of intracellular signaling pathways by specific types of Ca 2+ channels depends on localization of specific Ca 2+ receptors close to the channel mouth. The dual regulation of signaling pathways by Ca 2+ near channels and in the nucleus may permit neurons to precisely tailor transcriptional activation to specific types of electrical or chemical stimuli and at the same time ensure that only robust stimuli that generate nuclear Ca 2+ elevations are converted into long-term changes in gene expression.