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Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission

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Abstract

FAST synaptic transmission in the central nervous system can be modulated by neurotransmitters and second-messenger pathways. For example, transmission at glutamatergic synapses can be depressed by the metabotropic glutamate receptor1,2, providing autoreceptor-mediated negative feedback. Metabotropic glutamate receptor inhibition of Ca2+ channels may contribute to this pathway3–6. In contrast, stimulation of protein kinase C can enhance excitatory synaptic transmission7, whereas both depression and enhancement of Ca2+ current have been reported8. Here we show that in hippocampal CA3 and cortical pyramidal neurons, activation of protein kinase C enhances current through N-type Ca2+ channels and, in addition, dramatically reduces G protein-dependent inhibition of these same channels by the meta-botropic glutamate receptor. In parallel experiments on fast excitatory transmission at corticostriatal synapses, kinase C activators were similarly found to reduce the inhibitory effect produced by stimulation of the metabotropic glutamate receptor. The results show that second-to-second control of Ca2+ channels by the metabotropic glutamate receptor can itself be modulated on a slower timescale by protein kinase C. These mechanisms may be used in the control of fast excitatory synaptic transmission.

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Authors and Affiliations

  1. Department of Neurobiology, Harvard Medical School, Boston, Massachussetts, 02115, USA

    Kenton J. Swartz & Bruce P. Bean

  2. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA

    Andrew Merritt & David M. Lovinger

Authors
  1. Kenton J. Swartz
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  2. Andrew Merritt
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  3. Bruce P. Bean
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  4. David M. Lovinger
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Swartz, K., Merritt, A., Bean, B. et al. Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission. Nature 361, 165–168 (1993). https://doi.org/10.1038/361165a0

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