Regulation of Presynaptic NMDA Responses by External and Intracellular pH Changes at Developing Neuromuscular Synapses

Chen, Yu-Hwa; Wu, Mei-Lin; Fu, Wen‐Mei

doi:10.1523/jneurosci.18-08-02982.1998

Cited by 33 publications

(32 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many voltage-and ligand-gated ion channels that control membrane excitability are sensitive to changes in cellular pH (1)(2)(3). Neurotransmitter release and uptake are also influenced by cellular and organellar pH (4,5). Moreover, the intra-and extracellular pH of both neurons and glia are modulated in a highly transient and localized manner by neuronal activity (6,7).…”

mentioning

confidence: 99%

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Diering

Church

Numata

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

NHE5 is a brain-enriched Na ؉ /H؉ exchanger that dynamically shuttles between the plasma membrane and recycling endosomes, serving as a mechanism that acutely controls the local pH environment. In the current study we show that secretory carrier membrane proteins (SCAMPs), a group of tetraspanning integral membrane proteins that reside in multiple secretory and endocytic organelles, bind to NHE5 and co-localize predominantly in the recycling endosomes. In vitro protein-protein interaction assays revealed that NHE5 directly binds to the N-and C-terminal cytosolic extensions of SCAMP2. Heterologous expression of SCAMP2 but not SCAMP5 increased cell-surface abundance as well as transporter activity of NHE5 across the plasma membrane. Expression of a deletion mutant lacking the SCAMP2-specific N-terminal cytosolic domain, and a mini-gene encoding the N-terminal extension, reduced the transporter activity. Although both Arf6 and Rab11 positively regulate NHE5 cell-surface targeting and NHE5 activity across the plasma membrane, SCAMP2-mediated surface targeting of NHE5 was reversed by dominant-negative Arf6 but not by dominant-negative Rab11. Together, these results suggest that SCAMP2 regulates NHE5 transit through recycling endosomes and promotes its surface targeting in an Arf6-dependent manner.

show abstract

mentioning

confidence: 99%

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Diering

Church

Numata

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The similar pH effect on IPSC frequency still retained in mIPSCs after blockade of action potential-evoked IPSCs with TTX, indicating that constitutive GABA release at the presynaptic terminal is also regulated by extracellular pH. In fact, extracellular pH affects the frequency of miniature GABAergic or glycinergic IPSC (Li et al, 2003, Mozrzymas et al, 2003, Zhou et al, 2007) and NMDA EPSC (Chen et al, 1998) in a similar manner, further supporting the idea that proton-mediated basal neurotransmitter release may be mediated by a universal mechanism at presynaptic terminals. Voltage-gated Ca 2+ channels could be ideal candidates for the target considering the fact that external pH regulates voltage-dependent Ca 2+ channels (VDCCs), which involve in miniature neurotransmitter release via Ca 2+ channels-coupling to synaptic vesicle exocytosis (Otsu and Murphy, 2003).…”

Section: Discussionmentioning

confidence: 92%

Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus

Chen

Huang

2014

Neuroscience

View full text Add to dashboard Cite

Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15–26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 µM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1 mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells, The pH influence on GABAA receptors was similar in HEPES- and MES-buffered medium, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission, which is mediated by both presynaptic and postsynaptic mechanisms.

show abstract

“…Nowadays this is probably the most studied aspect of glutamatergic signaling in the neuromuscular synapse. A wide range of ionotropic glutamate receptors (kainate, AMPA and NMDA) has been found in synaptic contact in experiments on the culture of neurons and myocytes of Xenopus [72,82,83], and data indicate about predominantly presynaptic localization of these receptor structures. In the later stages of amphibians development, namely in tadpoles and adult frogs metabotropic glutamate receptors were found [80,[84][85][86], which, apparently, are localized postsynaptically [80,85].…”

Section: Glutamatergic Signalingmentioning

confidence: 99%

Non-Cholinergic Signaling Pathways at Vertebrate Neuromuscular Junctions

Malomouzh¹

2012

Skeletal Muscle - From Myogenesis to Clinical Relations

View full text Add to dashboard Cite

Regulation of Presynaptic NMDA Responses by External and Intracellular pH Changes at Developing Neuromuscular Synapses

Cited by 33 publications

References 44 publications

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus

Non-Cholinergic Signaling Pathways at Vertebrate Neuromuscular Junctions

Contact Info

Product

Resources

About