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Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):635-40. doi: 10.1073/pnas.0811685106. Epub 2008 Dec 31.

G protein-activated inwardly rectifying potassium channels mediate depotentiation of long-term potentiation.

Author information

1
Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco, CA 94158, USA.

Abstract

Excitatory synapses in the brain undergo activity-dependent changes in the strength of synaptic transmission. Such synaptic plasticity as exemplified by long-term potentiation (LTP) is considered a cellular correlate of learning and memory. The presence of G protein-activated inwardly rectifying K(+) (GIRK) channels near excitatory synapses on dendritic spines suggests their possible involvement in synaptic plasticity. However, whether activity-dependent regulation of GIRK channels affects excitatory synaptic plasticity is unknown. In a companion article we have reported activity-dependent regulation of GIRK channel density in cultured hippocampal neurons that requires activity of NMDA receptors (NMDAR) and protein phosphatase-1 (PP1) and takes place within 15 min. In this study, we performed whole-cell recordings of cultured hippocampal neurons and found that NMDAR activation increases basal GIRK current and GIRK channel activation mediated by adenosine A(1) receptors, but not GABA(B) receptors. Given the similar involvement of NMDARs, adenosine A(1) receptors, and PP1 in depotentiation of LTP caused by low-frequency stimulation that immediately follows LTP-inducing high-frequency stimulation, we wondered whether NMDAR-induced increase in GIRK channel surface density and current may contribute to the molecular mechanisms underlying this specific depotentiation. Remarkably, GIRK2 null mutation or GIRK channel blockade abolishes depotentiation of LTP, demonstrating that GIRK channels are critical for depotentiation, one form of excitatory synaptic plasticity.

PMID:
19118199
PMCID:
PMC2613041
DOI:
10.1073/pnas.0811685106
[Indexed for MEDLINE]
Free PMC Article

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