PMID: 7541535Jul 3, 1995Paper

Presynaptic modulation of cortical synaptic activity by calcineurin

Proceedings of the National Academy of Sciences of the United States of America
R G VictorB O'Rourke

Abstract

Synaptic plasticity is modulated by Ca(2+)-induced alterations in the balance between phosphorylation and dephosphorylation. Recent evidence suggests that calcineurin, the Ca(2+)-calmodulin-dependent phosphatase (2B), modulates the activity of postsynaptic glutamate receptors. However, in rat cortex, calcineurin is enriched mainly in presynaptic, not postsynaptic, fractions. To determine if calcineurin modulates glutamatergic neurotransmission through a presynaptic mechanism, we used whole-cell patch clamp experiments to test effects of two specific calcineurin inhibitors, cyclosporin A (CsA) and FK506, on synaptic activity in fetal rat cortical neurons. The rate of spontaneous action-potential firing was markedly increased by either CsA or FK506 but was unaffected by rapamycin, a structural analog of FK506 which has no effect on calcineurin. In voltage-clamp experiments, CsA increased the rate but not the amplitude of glutamate receptor-mediated, excitatory postsynaptic currents, suggesting an increased rate of glutamate release. CsA had no effect on the amplitude of currents evoked by brief bath application of selective glutamate receptor agonists, providing further evidence for a pre- rather than postsynaptic site of action....Continue Reading

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Citations

Nov 19, 2003·Biochemical and Biophysical Research Communications·Isabelle M Mansuy
Nov 12, 2003·Pharmacology & Therapeutics·Farzad Moien-AfshariIsmail Laher
Aug 27, 1997·European Journal of Pharmacology·M KageyamaA Kanai
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May 13, 1999·Progress in Neurobiology·M MoriokaE Miyamoto
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May 15, 2012·Epilepsia·Aristea S GalanopoulouCarlos Cepeda
Mar 20, 2008·Clinical Journal of the American Society of Nephrology : CJASN·Dianne B McKay, Michelle A Josephson
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·A SíkT F Freund
Jan 5, 2016·Trends in Neurosciences·Abhishek BanerjeeOle Paulsen
Nov 26, 2008·Brain & Development·Valerio NapolioniPaolo Curatolo
May 20, 2003·Journal of Neurochemistry·S D KuipersG J Ter Horst
Apr 7, 2009·Journal of Thrombosis and Haemostasis : JTH·L H NolascoK V Vijayan
Apr 20, 2004·Journal of Cellular and Molecular Medicine·Bozena KaminskaMalgorzata Zawadzka
May 17, 2008·CNS Neuroscience & Therapeutics·Germán Sierra-Paredes, Germán Sierra-Marcuño
Apr 27, 2011·Journal of Neurochemistry·Wei-Li ZhuLin Lu
Oct 27, 2006·Biochimica Et Biophysica Acta·Guy L OdomJeffrey S Chamberlain
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Jun 26, 2010·Journal of Hypertension·Inge H H T KleinPeter J Blankestijn
Aug 12, 2010·Journal of Hypertension·Markus P Schlaich, Guido Grassi

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