scholarly journals Comparison of Steroid Modulation of Spontaneous Inhibitory Postsynaptic Currents in Cultured Hippocampal Neurons and Steady-State Single-Channel Currents from Heterologously Expressed α1β2γ2L GABAA Receptors

2016 ◽  
Vol 89 (4) ◽  
pp. 399-406 ◽  
Author(s):  
Sampurna Chakrabarti ◽  
Mingxing Qian ◽  
Kathiresan Krishnan ◽  
Douglas F. Covey ◽  
Steven Mennerick ◽  
...  
Keyword(s):  
Steady State ◽  
Gabaa Receptors ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Steroid Modulation ◽  
Single Channel Currents ◽  
Channel Currents ◽  
Cultured Hippocampal Neurons

Potassium channels activated by GABAB agonists and serotonin in cultured hippocampal neurons

1994 ◽  
Vol 71 (6) ◽  
pp. 2570-2575 ◽  
Author(s):  
L. S. Premkumar ◽  
P. W. Gage
Keyword(s):  
Potassium Channels ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Gamma Aminobutyric Acid ◽  
Kinetic Behavior ◽  
Open Time ◽  
Voltage Dependent ◽  
Single Channel Currents ◽  
Channel Currents ◽  
Cultured Hippocampal Neurons

1. Single-channel currents were recorded in cell-attached patches on cultured hippocampal neurons in response to gamma-aminobutyric acid-B (GABAB) agonists or serotonin applied to the cell surface outside the patch area. 2. The channels activated by GABAB agonists and serotonin were potassium selective but had a different conductance and kinetic behavior. Channels activated by GABAB agonists had a higher conductance, longer open-time, and longer burst-length than channels activated by serotonin. 3. The kinetic behavior of channels activated by GABAB agonists varied with potential whereas channels activated by serotonin did not show voltage-dependent changes in kinetics. 4. In a few cell-attached patches, both types of channel were activated when the cell was exposed to GABA together with serotonin. 5. It was concluded that GABAB agonists and serotonin activate different potassium channels in the soma of cultured hippocampal neurons.

Gadolinium Reduces AMPA Receptor Desensitization and Deactivation in Hippocampal Neurons

2001 ◽  
Vol 86 (1) ◽  
pp. 173-182 ◽  
Author(s):  
Saobo Lei ◽  
John F. MacDonald
Keyword(s):  
Steady State ◽  
Ampa Receptor ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Single Channel ◽  
Trivalent Cation ◽  
Receptor Desensitization ◽  
Whole Cell ◽  
Low Concentrations ◽  
Cultured Hippocampal Neurons

The actions of the trivalent cation Gd3+ on whole cell AMPA receptor-mediated currents were studied in isolated hippocampal neurons, in nucleated or outside-out patches taken from cultured hippocampal neurons, and on miniature excitatory postsynaptic currents (mEPSCs) recorded in cultured hippocampal neurons. Glutamate, AMPA, or kainate was employed to activate AMPA receptors. Applications of relatively low concentrations of Gd3+ (0.1–10 μM) substantially enhanced steady-state whole cell glutamate and kainate-evoked currents without altering peak currents, suggesting that desensitization was reduced. However, higher concentrations (>30 μM) depressed steady-state currents, indicating an underlying inhibition of channel activity. Lower concentrations of Gd3+also increased the potency of peak glutamate-evoked currents without altering that of steady-state currents. An ultrafast perfusion system and nucleated patches were then used to better resolve peak glutamate-evoked currents. Low concentrations of Gd3+ reduced peak currents, enhanced steady-state currents, and slowed the onset of desensitization, providing further evidence that this cation reduces desensitization. In the presence of cyclothiazide, a compound that blocks desensitization, a low concentration Gd3+ inhibited both peak and steady-state currents, indicating that Gd3+ both reduces desensitization and inhibits these currents. Gd3+ reduced the probability of channel opening at the peak of the currents but did not alter the single channel conductance calculated using nonstationary variance analysis. Recovery from desensitization was enhanced, and glutamate-evoked current activation and deactivation were slowed by Gd3+. The Gd3+-induced reduction in desensitization did not require the presence of the GluR2 subunit as this effect was seen in hippocampal neurons from GluR2 null-mutant mice. Gd3+ reduced the time course of decay of mEPSCs perhaps as a consequence of its slowing of AMPA receptor deactivation although an increase in the frequency of mEPSCs also suggested enhanced presynaptic release of transmitter. These results demonstrate that Gd3+ potently reduces AMPA receptor desensitization and mimics a number of the properties of the positive modulators of AMPA receptor desensitization such as cyclothiazide.

Evoked inhibitory postsynaptic currents in the dynamics of development of cultured hippocampal neurons of rats

1999 ◽  
Vol 31 (5) ◽  
pp. 304-309 ◽  
Author(s):  
E. V. Isaeva ◽  
V. G. Sidorenko ◽  
S. A. Fedulova ◽  
N. S. Veselovskii
Keyword(s):  
Hippocampal Neurons ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Cultured Hippocampal Neurons

Proton Modulation of α1β3δ GABAA Receptor Channel Gating and Desensitization

2004 ◽  
Vol 92 (3) ◽  
pp. 1577-1585 ◽  
Author(s):  
Hua-Jun Feng ◽  
Robert L. Macdonald
Keyword(s):  
Steady State ◽  
Single Channel ◽  
Dependent Manner ◽  
Human Embryonic Kidney Cells ◽  
Receptor Isoforms ◽  
Long Duration ◽  
A Subunit ◽  
Single Channel Currents ◽  
Channel Currents ◽  
Receptor Channel

αβγ GABAA receptor currents are phasic and desensitizing, whereas αβδ GABAA receptor currents are tonic and have no fast desensitization. αβγ receptors are subsynaptic and mediate phasic inhibition, whereas αβδ receptors are extra- or perisynaptic and mediate tonic inhibition. Given the different roles of these GABAA receptor isoforms and the fact that GABAA receptors are allosterically regulated by extracellular pH in a subunit-dependent manner, we compared the effects of changing pH on rat δ or γ2L subunit–containing GABAA receptor currents. Human embryonic kidney cells (HEK293T) were transfected with cDNAs encoding rat α1, β3, γ2L, or δ GABAA receptor subunits in several binary and ternary combinations, and whole cell and single channel patch-clamp recordings were obtained. Lowering pH substantially enhanced α1β3 receptor currents. This effect was significantly more pronounced for ternary α1β3δ receptors, whereas ternary α1β3γ2L receptors were relatively insensitive to lowered pH. Lowering pH did not affect the extent of desensitization of α1β3 and α1β3γ2L receptor currents, but significantly increased the extent of desensitization of α1β3δ receptor currents. Lowering pH prolonged deactivation of α1β3 and α1β3δ receptor currents and enhanced the “steady-state” currents of α1β3δ receptors evoked by long-duration (28 s) GABA applications. Lowering pH significantly increased mean open duration of α1β3δ steady-state single channel currents due to introduction of a longer-duration open state, suggesting that low pH enhances α1β3δ receptor steady-state currents by modifying GABAA receptor gating properties.

Gabapentin Increases a Tonic Inhibitory Conductance in Hippocampal Pyramidal Neurons

2006 ◽  
Vol 105 (2) ◽  
pp. 325-333 ◽  
Author(s):  
Victor Y. Cheng ◽  
Robert P. Bonin ◽  
Mary W. Chiu ◽  
J Glen Newell ◽  
John F. MacDonald ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Hippocampal Neurons ◽  
Gabab Receptors ◽  
Gamma Aminobutyric Acid ◽  
Western Blots ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Inhibitory Conductance ◽  
Tonic Current

Background The mechanisms underlying the therapeutic actions of gabapentin remain poorly understood. The chemical structure and behavioral properties of gabapentin strongly suggest actions on inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA); however, gabapentin does not directly modulate GABAA or GABAB receptors. Two distinct forms of GABAergic inhibition occur in the brain: postsynaptic conductance and a persistent tonic inhibitory conductance primarily generated by extrasynaptic GABAA receptors. The aim of this study was to determine whether gabapentin increased the tonic conductance in hippocampal neurons in vitro. As a positive control, the effects of vigabatrin, which irreversibly inhibits GABA transaminase, were also examined. Methods GABAA receptors in hippocampal neurons from embryonic mice were studied using whole cell patch clamp recordings. Miniature inhibitory postsynaptic currents and the tonic current were recorded from cultured neurons that were treated for 36-48 h with gabapentin, vigabatrin, or gabapentin and vigabatrin. To determine whether gabapentin increased the expression of GABAA receptors, Western blots were stained with antibodies selective for alpha1, alpha2, and alpha5 subunits. Results GABAA receptors were insensitive to the acute application of gabapentin, whereas chronic treatment increased the amplitude of the tonic current threefold (EC50 = 209 microm) but did not influence miniature inhibitory postsynaptic currents. Vigabatrin increased the tonic conductance, and the maximally effective concentration did not occlude the actions of gabapentin, which suggests that these compounds act by different mechanisms. Neither gabapentin nor vigabatrin increased the expression of GABAA receptors in the neurons. Conclusions Gabapentin increases a tonic inhibitory conductance in mammalian neurons. High-affinity GABAA receptors that generate the tonic conductance may detect small increases in the ambient concentration of neurotransmitter caused by gabapentin.

Distributions of interevent intervals for miniature inhibitory and excitatory postsynaptic currents in cultured hippocampal neurons

2000 ◽  
Vol 32 (3) ◽  
pp. 158-160
Author(s):  
M. A. Chvanov ◽  
Ya. A. Boychuk ◽  
I. V. Melnick ◽  
P. V. Belan ◽  
P. G. Kostyuk
Keyword(s):  
Hippocampal Neurons ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Cultured Hippocampal Neurons
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