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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lovinger, D. M. Neurosci. Lett 129, 17–21 (1991).
Baskys, A. & Malenka, R. C. J. Physiol., Lond. 444, 687–701 (1991).
Lester, R. A. & Jahr, C. E. Neuron 4, 741–749 (1990).
Swartz, K. J. & Bean, B. P. J. Neurosci. 12, 4358–4371 (1992).
Sayer, R. J., Schwindt, P. C. & Crill, W. E. J. Neurophysiol. 68, 833–842 (1992).
Sahara, Y. & Westbrook, G. L. Soc. Neurosci. 17, 1168 (1991).
Malenka, R. C., Madison, D. V. & Nicoll, R. A. Nature 321, 175–177 (1986).
Anwyl, R. Brain Res. Rev. 16, 265–281 (1991).
Palmer, E. et al. Eur. J. Pharmac. 166, 585–587 (1988).
Irving, A. J. et. al. Eur. J. Pharmac. 186, 363–365 (1990).
House, C. & Kemp, B. E. Science 238, 1726–1728 (1987).
Olivera, B. M. et al. Science 230, 1338–1343 (1985).
Plummer, M. R., Logothetis, D. E. & Hess, P. Neuron 2, 1453–1463 (1989).
Aosaki, T. & Kasai, H. Pflügers Arch. 414, 150–156 (1989).
Regan, L. J., San, D. W. Y. & Bean, B. P. Neuron 6, 269–280 (1991).
Lipscombe, D., Bley, K. & Tsien, R. W. Soc. Neurosci. 14, 153 (1988).
Madison, D. V. Soc. Neurosci. 15, 16 (1989).
O'Dell, T. J. & Alger, B. E. J. Physiol., Lond. 436, 739–767 (1991).
Hirning, L. D. et al. Science 239, 57–61 (1988).
Kamiya, H., Sawada, S. & Yamamoto, C. Neurosci. Lett. 91, 84–88 (1988).
Horne, A. L. & Kemp, J. A. Br. J. Pharmac. 103, 1733–1739.
Cordingley, G. E. & Weight, F. F. Br. J. Pharmac. 88, 847–856 (1986).
North, R. A. Br. J. Pharmac. 98, 13–28 (1989).
Scholz, K. P. & Miller, R. J. Neuron 8, 1139–1150 (1992).
Dutar, P. & Nicoll, R. A. Neuron 1, 585–591 (1988).
Thompson, S. M., Haas, H. L. & Gahwiler, B. H. J. Physiol., Lond. 451, 347–363 (1992).
Leeb-Lundberg, L. M. F. et al. Proc. natn. Acad. Sci. U.S.A. 82, 5651–5655 (1985).
Pollock, W. K. & MacIntyre, D. E. Biochem. J. 234, 67–73 (1986).
Schoepp, D. D. & Johnson, B. G. Biochem. Pharmac. 37, 4299–4305 (1988).
Aramori, I. & Nakanishi, S. Neuron 8, 757–765 (1992).
Katada, T. et al. Eur. J. Biochem. 151, 431–437 (1985).
Bollag, G. E. et al. Proc. natn. Acad. Sci. U.S.A. 83, 5822–5824 (1986).
Bosma, M. M. & Hille, B. Proc. natn. Acad. Sci. U.S.A. 86, 2943–2947 (1989).
Rane, S. G. et al. Neuron 3, 239–245 (1989).
Hamill, O. P. et al. Pflügers Arch. 391, 85–100 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/361165a0
This article is cited by
-
N-Type Voltage Gated Calcium Channels Mediate Excitatory Synaptic Transmission in the Anterior Cingulate Cortex of Adult Mice
Molecular Pain (2013)
-
A PKCε–ENH–channel complex specifically modulates N-type Ca2+ channels
Nature Neuroscience (2003)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.