In vivo activation of kainate receptors induces dephosphorylation of the heavy neurofilament subunit.

Injection of kainic acid (KA) into the rat hippocampus reduced the phosphorylation-related immunoreactivity of the heavy subunit of neurofilament proteins (NF-H). The effect was demonstrated quantitatively with a dot-immunobinding assay and qualitatively by immunoblotting with monoclonal antibodies against phosphorylation-dependent and nonphosphorylation-related epitopes of NF-H. The KA-induced reduction affected 50% of the phosphorylated NF-H in half of the hippocampus after 48 h. At the same time, the nonphosphorylation-related NF-H immunoreactivity increased as revealed by immunoblotting, indicating a shift from phosphorylated to nonphosphorylated NF-H. The effects on NF-H preceded a decrease in content of the neuron-specific enolase, a soluble neuronal cytoplasmic protein. No alterations of the light subunit of neurofilament proteins occurred, suggesting that KA has a preferential effect on NF-H phosphorylation. N-Methyl-D-aspartate administered similarly did not lead to a rapid dephosphorylation of NF-H. We propose that kainate receptor-mediated dephosphorylation in NF-H is involved in the signal transduction of excitatory amino acids with consequences for neuronal functions dependent on intermediary filament phosphorylation.