Calcium-Sensitive Translocation of Calmodulin and Neurogranin between Soma and Dendrites of Mouse Hippocampal CA1 Neurons

Calmodulin (CaM) and neurogranin (Ng) are two abundant neuronal proteins whose interactions are implicated in the regulation of synaptic responses and plasticity. We employed the "low-calcium" model of epilepsy in hippocampal slices to investigate the mobilization of these two proteins in CA1 pyramidal neurons. Perfusion of mouse hippocampal slices with Ca(2+)-free artificial CSF (ACSF) caused a suppression of synaptic transmission and generation of epileptic activity; these responses could be reversed by normal Ca(2+)-containing ACSF. Fluorescence immunochemical staining of control hippocampal slices bathed in normal ACSF revealed that CaM and Ng were more concentrated in soma than in dendrites; especially for CaM, it was concentrated in the nucleus. Perfusion of hippocampal slices with Ca(2+)-free ACSF caused translocation of these two proteins from soma to dendrites, and this trafficking was also reversed by Ca(2+)-containing buffer. A reduction of ∼15 and 40 nM intracellular Ca(2+), [Ca(2+)](i), caused half-maximum translocation of Ng and CaM, respectively. Hippocampal CA1 pyramidal neurons were the most responsive to this Ca(2+)-sensitive translocation as compared to those from other areas of the hippocampus. These results illustrated the unique feature of hippocampal CA1 pyramidal neurons in sequestering high concentrations of CaM and Ng in soma and releasing them to distal dendrites at reducing level of [Ca(2+)](i).