AKAP150-anchored PKA activity is important for LTD during its induction phase

Yuan Lu; Mingxu Zhang; Indra A Lim; Duane D Hall; Margaret Allen; Yuliya Medvedeva; G Stanley McKnight; Yuriy M Usachev; Johannes W Hell

doi:10.1113/jphysiol.2008.151662

Back

AKAP150-anchored PKA activity is important for LTD during its induction phase

Journal article

Open access

Peer reviewed

AKAP150-anchored PKA activity is important for LTD during its induction phase

Yuan Lu, Mingxu Zhang, Indra A Lim, Duane D Hall, Margaret Allen, Yuliya Medvedeva, G Stanley McKnight, Yuriy M Usachev and Johannes W Hell

The Journal of physiology, Vol.586(17), pp.4155-4164

09/01/2008

DOI: 10.1113/jphysiol.2008.151662

PMCID: PMC2652176

PMID: 18617570

Files and links (1)

url

https://doi.org/10.1113/jphysiol.2008.151662View

Published (Version of record) Open Access

Abstract

Protein kinase A (PKA) is thought to tonically maintain an enhanced level of postsynaptic AMPA receptor responses. Injection of PKA inhibitory peptides leads to a run-down of AMPA receptor responses and prevents long-term depression (LTD). This run-down of AMPA receptor activity was proposed to occlude a further reduction that would otherwise constitute LTD. PKA is recruited to postsynaptic sites by the A kinase anchor protein AKAP150. We found that LTD was strongly impaired in acute hippocampal slices from 2-week-old mice in which the PKA binding site on AKAP150 had been genetically deleted (D36 mice). However, basal postsynaptic AMPA and NMDA receptor activity was indistinguishable between D36 and WT mice. During extracellular recordings of field EPSPs and during intracellular recording of EPSCs from hippocampal slices from WT mice, H-89 and KT5720, two structurally different PKA inhibitors, inhibited LTD by more than 70% without affecting basal synaptic transmission or basal phosphorylation of serine 845 on GluR1. Collectively our data indicate that AKAP150-anchored PKA activity is required to induce LTD and not merely to maintain a tonically heightened activity level of AMPA receptors as proposed earlier.

Cyclic AMP-Dependent Protein Kinases - metabolism

Long-Term Synaptic Depression - genetics

Long-Term Synaptic Depression - physiology

Male

Hippocampus - cytology

Sulfonamides - pharmacology

A Kinase Anchor Proteins - genetics

Pyrroles - pharmacology

Animals

Isoquinolines - pharmacology

Gene Deletion

Mice

Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors

Carbazoles - pharmacology

Hippocampus - physiology

Details

Title: Subtitle: AKAP150-anchored PKA activity is important for LTD during its induction phase
Creators: Yuan Lu - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242-1109, USA
Mingxu Zhang
Indra A Lim
Duane D Hall
Margaret Allen
Yuliya Medvedeva
G Stanley McKnight
Yuriy M Usachev
Johannes W Hell
Resource Type: Journal article
Publication Details: The Journal of physiology, Vol.586(17), pp.4155-4164
Publisher: England
DOI: 10.1113/jphysiol.2008.151662
PMID: 18617570
PMCID: PMC2652176
ISSN: 0022-3751
eISSN: 1469-7793
Grant note: R01 GM032875 / NIGMS NIH HHS NS035563 / NINDS NIH HHS P01 DA015916 / NIDA NIH HHS R01 NS054614 / NINDS NIH HHS NS054614 / NINDS NIH HHS GM032875 / NIGMS NIH HHS T32 GM008692 / NIGMS NIH HHS R01 NS035563 / NINDS NIH HHS R01 NS046450 / NINDS NIH HHS DA015916 / NIDA NIH HHS NS046450 / NINDS NIH HHS
Language: English
Date published: 09/01/2008
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984070416902771

Metrics

22 Record Views

60 Times Cited - Web of Science