Back to Search
Start Over
Postsynaptic NO/cGMP increases NMDA receptor currents via hyperpolarization-activated cyclic nucleotide-gated channels in the hippocampus.
- Source :
-
Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2014 Jul; Vol. 24 (7), pp. 1923-36. Date of Electronic Publication: 2013 Feb 28. - Publication Year :
- 2014
-
Abstract
- The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling cascade participates in the modulation of synaptic transmission. The effects of NO are mediated by the NO-sensitive cGMP-forming guanylyl cyclases (NO-GCs), which exist in 2 isoforms with indistinguishable regulatory properties. The lack of long-term potentiation (LTP) in knock-out (KO) mice deficient in either one of the NO-GC isoforms indicates the contribution of both NO-GCs to LTP. Recently, we showed that the NO-GC1 isoform is located presynaptically in glutamatergic neurons and increases the glutamate release via hyperpolarization-activated cyclic nucleotide (HCN)-gated channels in the hippocampus. Electrophysiological analysis of hippocampal CA1 neurons in whole-cell recordings revealed a reduction of HCN currents and a hyperpolarizing shift of the activation curve in the NO-GC2 KOs associated with reduced resting membrane potentials. These features were mimicked in wild-type (WT) neurons with an NO-GC inhibitor. Analysis of glutamate receptors revealed a cGMP-dependent reduction of NMDA receptor currents in the NO-GC2 KO mice, which was mimicked in WT by HCN channel inhibition. Lowering extracellular Mg(2+) increased NMDA receptor currents in the NO-GC2 KO and allowed the induction of LTP that was absent at physiological Mg(2+). In sum, our data indicate that postsynaptic cGMP increases the N-methyl-D-aspartate (NMDA) receptor current by gating HCN channels and thereby is required for LTP.<br /> (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Anesthetics, Local pharmacology
Animals
Animals, Newborn
Cyclic GMP pharmacology
Electric Stimulation
Excitatory Amino Acid Antagonists pharmacology
Guanylate Cyclase genetics
Guanylate Cyclase metabolism
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels metabolism
In Vitro Techniques
Lidocaine analogs & derivatives
Lidocaine pharmacology
Long-Term Potentiation drug effects
Mice
Mice, Knockout
Neurons drug effects
Nitric Oxide genetics
Patch-Clamp Techniques
Pyrimidines pharmacology
Tetraethylammonium pharmacology
CA1 Region, Hippocampal cytology
Cyclic GMP metabolism
Long-Term Potentiation physiology
Neurons physiology
Nitric Oxide deficiency
Receptors, N-Methyl-D-Aspartate metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2199
- Volume :
- 24
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cerebral cortex (New York, N.Y. : 1991)
- Publication Type :
- Academic Journal
- Accession number :
- 23448871
- Full Text :
- https://doi.org/10.1093/cercor/bht048