Cell Type-Specific Expression of Acid-Sensing Ion Channels in Hippocampal Interneurons

Weng, Ju Yun; Lin, Yen Chu; Lien, Cheng Chang

doi:10.1523/jneurosci.0582-10.2010

Cited by 66 publications

(76 citation statements)

References 51 publications

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“…ASIC1a is expressed throughout the brain, with prominent expression in areas that receive rich synaptic input [17], [20], [22], [23]. Moreover, ASIC1a have a higher expression in GABAergic interneurons than that in the principal neurons [7], [24]. Given that the GABA A receptors are the predominant inhibitory ionotropic receptors in the CNS, the interaction between ASIC1a and GABA A receptors may occur at numerous locations and could be involved in a number of brain functions.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Protein Complex Containing ASIC1a and GABAA Receptors and Their Interregulation

et al. 2014

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Acid-sensing ion channels (ASICs) belong to the family of the epithelial sodium channel/degenerin (ENaC/DEG) and are activated by extracellular protons. They are widely distributed within both the central and peripheral nervous systems. ASICs were modified by the activation of γ-aminobutyric acid receptors (GABAA), a ligand-gated chloride channels, in hippocampal neurons. In contrast, the activity of GABAA receptors were also modulated by extracellular pH. However so far, the mechanisms underlying this intermodulation remain obscure. We hypothesized that these two receptors-GABAA receptors and ASICs channels might form a novel protein complex and functionally interact with each other. In the study reported here, we found that ASICs were modified by the activation of GABAA receptors either in HEK293 cells following transient co-transfection of GABAA and ASIC1a or in primary cultured dorsal root ganglia (DRG) neurons. Conversely, activation of ASIC1a also modifies the GABAA receptor-channel kinetics. Immunoassays showed that both GABAA and ASIC1a proteins were co-immunoprecipitated mutually either in HEK293 cells co-transfected with GABAA and ASIC1a or in primary cultured DRG neurons. Our results indicate that putative GABAA and ASIC1a channels functionally interact with each other, possibly via an inter-molecular association by forming a novel protein complex.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Protein Complex Containing ASIC1a and GABAA Receptors and Their Interregulation

et al. 2014

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“…The acid-evoked current in inhibitory neurons might be responsible (FIG. 4), as in the hippocampus, ASIC1A is more abundant in GABAergic neurons than in glutamatergic neurons 52,95,96 . It is also puzzling that other studies have raised the possibility that ASIC1A might have the opposite effect and increase seizure activity 15 .…”

Section: Asics Neurotoxicity and Neurological Diseasesmentioning

confidence: 98%

“…a | The ability of acidosis to inhibit seizures is thought to be acid-sensing ion channel 1A (ASIC1A)-mediated, possibly owing to abundant ASIC1A expression in GABAergic neurons 52,95,96 . b | Accumulating evidence suggests that acidosis potentiates cell death, which contributes to ischaemic stroke and neurodegenerative disease and that this depends on ASIC1A.…”

Section: Figurementioning

confidence: 99%

Acid-sensing ion channels in pain and disease

2013

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Why do neurons sense extracellular acid? In large part, this question has driven increasing investigation on acid-sensing ion channels (ASICs) in the CNS and the peripheral nervous system for the past two decades. Significant progress has been made in understanding the structure and function of ASICs at the molecular level. Studies aimed at clarifying their physiological importance have suggested roles for ASICs in pain, neurological and psychiatric disease. This Review highlights recent findings linking these channels to physiology and disease. In addition, it discusses some of the implications for therapy and points out questions that remain unanswered.

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“…Both CA1 pyramidal cells and dentate granule cells were visually selected for whole-cell patch recordings (pipette resistance 3-5 MΩ) under differential interference contrast optics (BX51WI, Olympus, Tokyo, Japan) using Multiclamp 700B or Axopatch 200B amplifiers (Molecular Devices, Union City, CA) as described [40]. Pipette capacitance was carefully compensated to >95%.…”

Section: Methodsmentioning

confidence: 99%

Cell Type-Specific Dependency on the PI3K/Akt Signaling Pathway for the Endogenous Epo and VEGF Induction by Baicalein in Neurons versus Astrocytes

Sun

Lin²,

Lin

et al. 2013

PLoS ONE

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The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

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Cell Type-Specific Expression of Acid-Sensing Ion Channels in Hippocampal Interneurons

Cited by 66 publications

References 51 publications

Identification of a Novel Protein Complex Containing ASIC1a and GABAA Receptors and Their Interregulation

Identification of a Novel Protein Complex Containing ASIC1a and GABAA Receptors and Their Interregulation

Acid-sensing ion channels in pain and disease

Cell Type-Specific Dependency on the PI3K/Akt Signaling Pathway for the Endogenous Epo and VEGF Induction by Baicalein in Neurons versus Astrocytes

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