GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus

Drake, Carrie T.; Bausch, Suzanne B.; Milner, Teresa A.; Chavkin, Charles

doi:10.1073/pnas.94.3.1007

Cited by 92 publications

(82 citation statements)

References 41 publications

(43 reference statements)

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“…Consistent with previous studies (Ponce et al, 1996;Drake et al, 1997;Luscher et al, 1997;Takigawa and Alzheimer, 1999;Chen and Johnston, 2005), we found GIRK1 and GIRK2 primarily in the dendritic compartment. GIRK1 and GIRK2 were found at extrasynaptic or perisynaptic sites of postsynaptic specialization in hippocampal CA1 neurons, reminiscent of the distribution of the GABA B receptor (Kulik et al, 2003).…”

Section: Discussionsupporting

confidence: 93%

Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels

Koyrakh¹,

Luján²,

Colón³

et al. 2005

J. Neurosci.

177

257

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Neuronal G-protein-gated potassium (GIRK) channels mediate the inhibitory effects of many neurotransmitters. Although the overlapping distribution of GIRK subunits suggests that channel composition varies in the CNS, little direct evidence supports the existence of structural or functional diversity in the neuronal GIRK channel repertoire. Here we show that the GIRK channels linked to GABA B receptors differed in two neuron populations. In the substantia nigra, GIRK2 was the principal subunit, and it was found primarily in dendrites of neurons in the substantia nigra pars compacta (SNc). Baclofen evoked prominent barium-sensitive outward current in dopamine neurons of the SNc from wild-type mice, but this current was completely absent in neurons from GIRK2 knock-out mice. In the hippocampus, all three neuronal GIRK subunits were detected. The loss of GIRK1 or GIRK2 was correlated with equivalent, dramatic reductions in baclofen-evoked current in CA1 neurons. Virtually all of the barium-sensitive component of the baclofen-evoked current was eliminated with the ablation of both GIRK2 and GIRK3, indicating that channels containing GIRK3 contribute to the postsynaptic inhibitory effect of GABA B receptor activation. The impact of GIRK subunit ablation on baclofen-evoked current was consistent with observations that GIRK1, GIRK2, and GABA B receptors were enriched in lipid rafts isolated from mouse brain, whereas GIRK3 was found primarily in higher-density membrane fractions. Altogether, our data show that different GIRK channel subtypes can couple to GABA B receptors in vivo. Furthermore, subunit composition appears to specify interactions between GIRK channels and organizational elements involved in channel distribution and efficient receptor coupling.

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Section: Discussionsupporting

confidence: 93%

Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels

Koyrakh¹,

Luján²,

Colón³

et al. 2005

J. Neurosci.

177

257

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“…Thus, depotentiation likely involves GIRK channel activation by postsynaptic A 1 receptors (11) in addition to modulation of AMPA receptor phosphorylation (6,27). Given that both GIRK channels (16,28) and A 1 receptors (18,19) reside on the dendritic spines and shafts, and that GIRK channel activation by adenosine attenuates the EPSP by Ϸ30% (21), LFS-induced NMDAR activation could lead to depotentiation by enhancing GIRK channel activation by A 1 receptors at or near excitatory synapses, thereby shunting the synaptic inputs (21,22) and/or back-propagating dendritic action potentials so as to dampen or reverse processes for the induction or expression of LTP (29,30).…”

Section: Nmdar Activation Increases Girk Current Stimulated By Adenosmentioning

confidence: 99%

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

Chung

Xiang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

108

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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 activitydependent 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 GABAB receptors. Given the similar involvement of NMDARs, adenosine A1 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.adenosine receptor ͉ synaptic plasticity ͉ learning and memory ͉ protein phosphatase-1 ͉ extracellular field recording S ynaptic plasticity, the ability of neurons to modify the efficacy of synaptic transmission, is thought to provide the cellular basis for the profound influence of experience over information processing and storage in the brain (1, 2). For example, long-term potentiation (LTP), a long-lasting increase in excitatory synaptic strength after heightened synaptic activity (3), is believed to be the cellular correlate of learning and memory. Since the discovery of LTP in the hippocampus, a region known to be essential for learning and memory, LTP has been extensively characterized for the molecular mechanisms of its induction and expression that involves Ca 2ϩ influx through NMDA receptors (NMDARs), leading to a high level of intracellular Ca 2ϩ concentration, and activation of calcium/calmodulin-dependent kinase II (CaMKII) (3).Whether the excitatory synaptic activities generated by highfrequency stimulation (HFS) result in LTP depends on the pattern of synaptic inputs impinging on the postsynaptic CA1 neurons shortly afterward; LTP of field excitatory postsynaptic potential (fEPSP) of CA1 neurons fails to develop if the HFS of the Schaffer collateral nerve fibers is followed within minutes by low-frequency stimulation (LFS) (4, 5). This form of synaptic plasticity, called depotentiation, may be a mechanism to abort the LTP according to events that take...

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“…The dendritic localization of GIRK channels has been shown in neocortical neurons with whole-cell recordings from isolated dendrites (Takigawa and Alzheimer, 1999). Less is known about GIRK channels in the dendritic membrane of CA1 pyramidal neurons, although immunoelectron microscopy studies have located GIRK1 proteins in the dendritic shaft and spines of these cells (Drake et al, 1997). In particular, no single-channel data are available for GIRK channels in intact CA1 neurons, nor is the spatial localization of these channels directly measured with dendritic recordings.…”

Section: Introductionmentioning

confidence: 99%

Constitutively Active G-Protein-Gated Inwardly Rectifying K⁺Channels in Dendrites of Hippocampal CA1 Pyramidal Neurons

Chen¹,

Johnston²

2005

J. Neurosci.

123

103

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A diversity of ion channels contributes to the active properties of neuronal dendrites. From the apical dendrites of hippocampal CA1 pyramidal neurons, we recorded inwardly rectifying K ϩ channels with a single-channel conductance of 33 pS. The inwardly rectifying K ϩ channels were constitutively active at the resting membrane potential. The amount of constitutive channel activity was significantly larger in the apical dendrites than in the soma. Activities of these inwardly rectifying K ϩ channels were inhibited by Ba 2ϩ (200 M) and tertiapin (10 nM), both of which are believed to block G-protein-coupled inwardly rectifying K ϩ (GIRK) channels. Intracellularly applied GTP␥S (20 M) during dual dendritic recordings significantly increased constitutive channel activity. Baclofen (20 M), an agonist for the G-protein-coupled GABA B receptor, also significantly increased the level of channel activity. Therefore, these channels are GIRK channels, which are constitutively active at rest in the apical dendrites of CA1 pyramidal neurons and can be further activated via G-proteincoupled neurotransmitter receptors.

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GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus

Cited by 92 publications

References 41 publications

Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels

Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels

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

Constitutively Active G-Protein-Gated Inwardly Rectifying K⁺Channels in Dendrites of Hippocampal CA1 Pyramidal Neurons

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GIRK1 immunoreactivity is present predominantly in dendrites, dendritic spines, and somata in the CA1 region of the hippocampus

Cited by 92 publications

References 41 publications

Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels

Molecular and Cellular Diversity of Neuronal G-Protein-Gated Potassium Channels

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

Constitutively Active G-Protein-Gated Inwardly Rectifying K+Channels in Dendrites of Hippocampal CA1 Pyramidal Neurons

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Constitutively Active G-Protein-Gated Inwardly Rectifying K⁺Channels in Dendrites of Hippocampal CA1 Pyramidal Neurons