We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Calcium dynamics are altered in cortical neurons lacking the calmodulin-binding protein RC3.
- Authors
Van Dalen, Jacqueline J. W.; Gerendasy, Dan D.; De Graan, Pierre N. E.; Schrama, Loes H.; Gruol, Donna L.
- Abstract
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 Ca2+ and calmodulin, and proposed mechanisms of RC3 action involve both molecules. However, physiological evidence for a role of RC3 in neuronal Ca2+ 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 Ca2+ imaging to investigate a role for RC3 in neuronal Ca2+ 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 γ-aminobutyric acid (GABA)ergic neurons. However, the absence of RC3 in the RC3-/- neurons was found to alter neuronal Ca2+ dynamics including baseline Ca2+ levels measured under normal physiological conditions or after blockade of synaptic transmission, spontaneous intracellular Ca2+ oscillations generated by network synaptic activity, and Ca2+ responses elicited by exogenous application of N-methyl-d-aspartate (NMDA) or class I metabotropic glutamate receptor agonists. Thus, significant changes in Ca2+ 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 Ca2+ dynamics.
- Subjects
CALCIUM-binding proteins; NEURONS
- Publication
European Journal of Neuroscience, 2003, Vol 18, Issue 1, p13
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1046/j.1460-9568.2003.02720.x