Effects of monomethyltin and dimethyltin compounds on heterologously expressed neuronal ion channels (Xenopus oocytes) and synaptic transmission (hippocampal slices)

2007 ◽  
Vol 28 (1) ◽  
pp. 114-125 ◽  
Author(s):  
K. Krüger ◽  
T. Höing ◽  
W. Bensch ◽  
V. Diepgrond ◽  
M. Ahnefeld ◽  
...  
Keyword(s):  
Ion Channels ◽  
Synaptic Transmission ◽  
Xenopus Oocytes ◽  
Hippocampal Slices

scholarly journals The Neuropeptide Nocistatin Is Not a Direct Agonist of Acid-Sensing Ion Channel 1a (ASIC1a)

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 571
Author(s):  
Sven Kuspiel ◽  
Dominik Wiemuth ◽  
Stefan Gründer
Keyword(s):  
Ion Channels ◽  
Synaptic Transmission ◽  
Ion Channel ◽  
Cho Cells ◽  
Xenopus Oocytes ◽  
Ionotropic Receptors ◽  
Bath Solution ◽  
Acid Sensing Ion Channels ◽  
Acidic Peptide

Acid-sensing ion channels (ASICs) are ionotropic receptors that are directly activated by protons. Although protons have been shown to act as a neurotransmitter and to activate ASICs during synaptic transmission, it remains a possibility that other ligands directly activate ASICs as well. Neuropeptides are attractive candidates for alternative agonists of ASICs, because related ionotropic receptors are directly activated by neuropeptides and because diverse neuropeptides modulate ASICs. Recently, it has been reported that the neuropeptide nocistatin directly activates ASICs, including ASIC1a. Here we show that nocistatin does not directly activate ASIC1a expressed in Xenopus oocytes or CHO cells. Moreover, we show that nocistatin acidifies the bath solution to an extent that can fully explain the previously reported activation by this highly acidic peptide. In summary, we conclude that nocistatin only indirectly activates ASIC1a via acidification of the bath solution.

scholarly journals Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons

2008 ◽  
Vol 99 (1) ◽  
pp. 122-132 ◽  
Author(s):  
Gary Tong ◽  
Hiroto Takahashi ◽  
Shichun Tu ◽  
Yeonsook Shin ◽  
Maria Talantova ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Xenopus Oocytes ◽  
Hippocampal Slices ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Mammalian Cell Lines ◽  
Induced Currents ◽  
Channel Properties ◽  
Two Populations

Expression of the NR3A subunit with NR1/NR2 in Xenopus oocytes or mammalian cell lines leads to a reduction in N-methyl-d-aspartate (NMDA)-induced currents and decreased Mg2+ sensitivity and Ca2+ permeability compared with NR1/NR2 receptors. Consistent with these findings, neurons from NR3A knockout (KO) mice exhibit enhanced NMDA-induced currents. Recombinant NR3A can also form excitatory glycine receptors with NR1 in the absence of NR2. However, the effects of NR3A on channel properties in neurons and synaptic transmission have not been fully elucidated. To study physiological roles of NR3A subunits, we generated NR3A transgenic (Tg) mice. Cultured NR3A Tg neurons exhibited two populations of NMDA receptor (NMDAR) channels, reduced Mg2+ sensitivity, and decreased Ca2+ permeability in response to NMDA/glycine, but glycine alone did not elicit excitatory currents. In addition, NMDAR-mediated excitatory postsynaptic currents (EPSCs) in NR3A Tg hippocampal slices showed reduced Mg2+ sensitivity, consistent with the notion that NR3A subunits incorporated into synaptic NMDARs. To study the function of endogenous NR3A subunits, we compared NMDAR-mediated EPSCs in NR3A KO and WT control mice. In NR3A KO mice, the ratio of the amplitudes of the NMDAR-mediated component to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated component of the EPSC was significantly larger than that seen in WT littermates. This result suggests that NR3A subunits contributed to the NMDAR-mediated component of the EPSC in WT mice. Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extrasynaptic receptors, likely composed of NR1, NR2, and NR3 subunits.

Two Mechanisms That Raise Free Intracellular Calcium in Rat Hippocampal Neurons During Hypoosmotic and Low NaCl Treatment

2000 ◽  
Vol 83 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Aren J. Borgdorff ◽  
George G. Somjen ◽  
Wytse J. Wadman
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Calcium ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Cell Swelling ◽  
Tissue Slices ◽  
Extracellular Medium ◽  
Calcium Activity ◽  
Hippocampal Pyramidal Neurons

Previous studies have shown that exposing hippocampal slices to low osmolarity (πo) or to low extracellular NaCl concentration ([NaCl]o) enhances synaptic transmission and also causes interstitial calcium ([Ca2+]o) to decrease. Reduction of [Ca2+]o suggests cellular uptake and could explain the potentiation of synaptic transmission. We measured intracellular calcium activity ([Ca2+]i) using fluorescent indicator dyes. In CA1 hippocampal pyramidal neurons in tissue slices, lowering πo by ∼70 mOsm caused “resting” [Ca2+]i as well as synaptically or directly stimulated transient increases of calcium activity (Δ[Ca2+]i) to transiently decrease and then to increase. In dissociated cells, lowering πo by ∼70 mOsm caused [Ca2+]i to almost double on average from 83 to 155 nM. The increase of [Ca2+]i was not significantly correlated with hypotonic cell swelling. Isoosmotic (mannitol- or sucrose-substituted) lowering of [NaCl]o, which did not cause cell swelling, also raised [Ca2+]i. Substituting NaCl with choline-Cl or Na-methyl-sulfate did not affect [Ca2+]i. In neurons bathed in calcium-free medium, lowering πo caused a milder increase of [Ca2+]i, which was correlated with cell swelling, but in the absence of external Ca2+, isotonic lowering of [NaCl]o triggered only a brief, transient response. We conclude that decrease of extracellular ionic strength (i.e., in both low πo and low [NaCl]o) causes a net influx of Ca2+ from the extracellular medium whereas cell swelling, or the increase in membrane tension, is a signal for the release of Ca2+ from intracellular stores.

Y5 Receptors Mediate Neuropeptide Y Actions at Excitatory Synapses in Area CA3 of the Mouse Hippocampus

2002 ◽  
Vol 87 (1) ◽  
pp. 558-566 ◽  
Author(s):  
Hui Guo ◽  
Peter A. Castro ◽  
Richard D. Palmiter ◽  
Scott C. Baraban
Keyword(s):  
Synaptic Transmission ◽  
Neuropeptide Y ◽  
Critical Role ◽  
Hippocampal Slices ◽  
Receptor Subtype ◽  
Limbic Seizures ◽  
Excitatory Transmission ◽  
Npy Receptor ◽  
Bath Application ◽  
Peptide Agonist

Neuropeptide Y (NPY) is a potent modulator of excitatory synaptic transmission and limbic seizures. NPY is abundantly expressed in the dentate gyrus and is thought to modulate hippocampal excitability via activation of presynaptic Y2 receptors (Y2R). Here we demonstrate that NPY, and commonly used Y2R-preferring (NPY13–36) and Y5 receptor (Y5R)–preferring ([d-Trp32]NPY and hPP) peptide agonists, evoke similar levels of inhibition at excitatory CA3 synapses in hippocampal slices from wild-type control mice (WT). In contrast, NPYergic inhibition of excitatory CA3 synaptic transmission is absent in mice lacking the Y5R subtype (Y5R KO). In both analyses of evoked population spike activity and spontaneous excitatory postsynaptic synaptic currents (EPSCs), NPY agonists induced powerful inhibitory effects in all hippocampal slices from WT mice, whereas these peptides had no effect in slices from Y5R KO mice. In slices from WT mice, NPY (and NPY receptor–preferring agonists) reduced the frequency of spontaneous EPSCs but had no effect on sEPSC amplitude, rise time, or decay time. Furthermore, NPYergic modulation of spontaneous EPSCs in WT mice was mimicked by bath application of a novel Y5R-selective peptide agonist ([cpp]hPP) but not the selective Y2R agonist ([ahx5–24]NPY). In situ hybridization was used to confirm the presence of NPY, Y2, and Y5 mRNA in the hippocampus of WT mice and the absence of Y5R in knockout mice. These results suggest that the Y5 receptor subtype, previously believed to mediate food intake, plays a critical role in modulation of hippocampal excitatory transmission at the hilar-to-CA3 synapse in the mouse.

Presynaptic Modulation of Synaptic Transmission by Pregnenolone Sulfate as Studied by Optical Recordings

2005 ◽  
Vol 94 (6) ◽  
pp. 4131-4144 ◽  
Author(s):  
Ling Chen ◽  
Masahiro Sokabe
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Optical Recording ◽  
Perforant Path ◽  
Dependent Manner ◽  
Pregnenolone Sulfate ◽  
Voltage Sensitive Dyes ◽  
Dose Dependent

The effects of pregnenolone sulfate (PREGS), a putative neurosteroid, on the transmission of perforant path–granule cell synapses were investigated with an optical recording technique in rat hippocampal slices stained with voltage-sensitive dyes. Application of PREGS to the bath solution resulted in an acute augmentation of EPSP in a dose-dependent manner. The PREGS effect was dependent on the extracellular Ca2+ concentration ([Ca2+]o), but independent of NMDA receptor activation. PREGS caused a decrease in paired-pulse facilitation, which implies that PREGS positively modulates presynaptic neurotransmitter releases. Firmer support for this mechanism was that PREGS augmented the synaptically induced glial depolarization (SIGD) that reflects the activity of electrogenic glutamate transporters in glial cells during the uptake of released glutamate. The selective α7nAChR antagonist α-BGT or MLA prevented the SIGD increase by PREGS. Furthermore DMXB, a selective α7nAChR agonist, mimicked the PREGS effect on SIGD and antagonized the effect of PREGS. The presynaptic effect of PREGS was partially attenuated by the L-type Ca2+ channel (VGCC) blocker nifedipine. Based on these findings, we proposed a novel mechanism underlying the facilitated synaptic transmission by PREGS: this neurosteroid sensitizes presynaptic α7nAChR that is followed by an activation of L-type VGCC to increase the presynaptic glutamate release.

scholarly journals KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

2006 ◽  
Vol 95 (5) ◽  
pp. 3105-3112 ◽  
Author(s):  
S. Piccinin ◽  
A. D. Randall ◽  
J. T. Brown
Keyword(s):  
Synaptic Transmission ◽  
High Frequency ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Neuronal Firing ◽  
Population Spike ◽  
Channel Blockers ◽  
Kv7 Channels ◽  
Population Spikes ◽  
Gamma Frequency

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ /Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30–80 Hz). Further increasing [K+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 μM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 μM) or XE-991 (10 μM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

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