Referenced in: none

Automatically associated channels: Kv2.1

Title: Calcium dynamics are altered in cortical neurons lacking the calmodulin-binding protein RC3.

Authors: Jacqueline J W van Dalen, Dan D Gerendasy, Pierre N E de Graan, Loes H Schrama, Donna L Gruol

Journal, date & volume: Eur. J. Neurosci., 2003 Jul , 18, 13-22

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12859333

Abstract
RC3 is a neuronal calmodulin-binding protein and protein kinase C substrate that is thought to play an important regulatory role in synaptic transmission and neuronal plasticity. Two molecules known to regulate synaptic transmission and neuronal plasticity are Ca(2+) and calmodulin, and proposed mechanisms of RC3 action involve both molecules. However, physiological evidence for a role of RC3 in neuronal Ca(2+) dynamics is limited. In the current study we utilized cultured cortical neurons obtained from RC3 knockout (RC3-/-) and wildtype mice (RC3+/+) and fura-2-based microscopic Ca(2+) imaging to investigate a role for RC3 in neuronal Ca(2+) dynamics. Immunocytochemical characterization showed that the RC3-/- cultures lack RC3 immunoreactivity, whereas cultures prepared from wildtype mice showed RC3 immunoreactivity at all ages studied. RC3+/+ and RC3-/- cultures were indistinguishable with respect to neuron density, neuronal morphology, the formation of extensive neuritic networks and the presence of glial fibrillary acidic protein (GFAP)-positive astrocytes and gamma-aminobutyric acid (GABA)ergic neurons. However, the absence of RC3 in the RC3-/- neurons was found to alter neuronal Ca(2+) dynamics including baseline Ca(2+) levels measured under normal physiological conditions or after blockade of synaptic transmission, spontaneous intracellular Ca(2+) oscillations generated by network synaptic activity, and Ca(2+) responses elicited by exogenous application of N-methyl-D-aspartate (NMDA) or class I metabotropic glutamate receptor agonists. Thus, significant changes in Ca(2+) dynamics occur in cortical neurons when RC3 is absent and these changes do not involve changes in gross neuronal morphology or neuronal maturation. These data provide direct physiological evidence for a regulatory role of RC3 in neuronal Ca(2+) dynamics.