ION CHANNELS: Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression

    loading  Checking for direct PDF access through Ovid

Abstract

Voltage-gated Cav1.2 channels (L-type calcium channel α1C subunits) are critical mediators of transcription-dependent neural plasticity. Whether these channels signal via the influx of calcium ion (Ca2+), voltage-dependent conformational change (VΔC), or a combination of the two has thus far been equivocal. We fused Cav1.2 to a ligand-gated Ca2+-permeable channel, enabling independent control of localized Ca2+ and VAC signals. This revealed an unexpected dual requirement: Ca2+ must first mobilize actin-bound Ca2+/calmodulin-dependent protein kinase II, freeing it for subsequent VΔC-mediated accumulation. Neither signal alone sufficed to activate transcription. Signal order was crucial: Efficiency peaked when Ca2+ preceded VΔC by 10 to 20 seconds. Cav1.2 VΔC synergistically augmented signaling by N-methyl-D-aspartate receptors. Furthermore, VΔC mistuning correlated with autistic symptoms in Timothy syndrome. Thus, nonionic VΔC signaling is vital to the function of Cav1.2 in synaptic and neuropsychiatric processes.

Related Topics

    loading  Loading Related Articles