scholarly journals Saikosaponin a Enhances Transient Inactivating Potassium Current in Rat Hippocampal CA1 Neurons

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Xie ◽  
Yun Hong Yu ◽  
Yong Ping Du ◽  
Yun Yan Zhao ◽  
Chang Zheng Li ◽  
...  
Keyword(s):  
Hippocampal Slices ◽  
Chinese Herb ◽  
Dependent Manner ◽  
Activation Curve ◽  
Ca1 Neurons ◽  
Epileptiform Discharges ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Dose Dependent ◽  
Saikosaponin A

Saikosaponin a (SSa), a main constituent of the Chinese herbBupleurum chinenseDC., has been demonstrated to have antiepileptic activity. Recent studies have shown that SSa could inhibit NMDA receptor current and persistent sodium current. However, the effects of SSa on potassium (K+) currents remain unclear. In this study, we tested the effect of SSa on 4AP-induced epileptiform discharges and K+currents in CA1 neurons of rat hippocampal slices. We found that SSa significantly inhibited epileptiform discharges frequency and duration in hippocampal CA1 neurons in the 4AP seizure model in a dose-dependent manner with anIC50of 0.7 μM. SSa effectively increased the amplitude ofITotalandIA, significantly negative-shifted the activation curve, and positive-shifted steady-state curve ofIA. However, SSa induced no significant changes in the amplitude and activation curve ofIK. In addition, SSa significantly increased the amplitude of 4AP-sensitive K+current, while there was no significant change in the amplitude of TEA-sensitive K+current. Together, our data indicate that SSa inhibits epileptiform discharges induced by 4AP in a dose-dependent manner and that SSa exerts selectively enhancing effects onIA. These increases inIAmay contribute to the anticonvulsant mechanisms of SSa.

TXA2 agonists inhibit high-voltage-activated calcium channels in rat hippocampal CA1 neurons

1996 ◽  
Vol 271 (4) ◽  
pp. C1269-C1277 ◽  
Author(s):  
K. S. Hsu ◽  
C. C. Huang ◽  
W. M. Kan ◽  
P. W. Gean
Keyword(s):  
Hippocampal Neurons ◽  
Cell Voltage ◽  
Specific Protein ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Whole Cell ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Alpha 7

Whole cell voltage clamp recordings were used to investigate the effects of thromboxane A2 (TXA2) agonists on the voltage-dependent Ca2+ currents in rat hippocampal CA1 neurons. TXA2 agonists [1S-[1 alpha, 2 beta(5Z), 3 alpha(1E, 3S*)4 alpha ]]-7-[3-[3-hydroxy-4-(4'-iodophenoxy)-1-butenyl]-7-oxabicyclo [2,2,1]heptan-2-yl]-5-heptenoic acid (I-BOP) and U-46619, reversibly suppressed the whole cell Ca2+ currents in a concentration-dependent manner. The effect was blocked by specific TXA2 receptor antagonist, SQ-29548. I-BOP as well as U-46619 inhibited both omega-conotoxin GVIA (CgTx)-sensitive and nimodipine sensitive Ca2+ currents but had no effect on CgTx/nimodipine insensitive Ca2+ currents. The I-BOP and U-46619 inhibition of Ca2+ currents was blocked by internal dialysis of hippocampal neurons with specific protein kinase C (PKC) inhibitors, NPC-15437 and PKC inhibitor-(19-36). Pretreatment of hippocampal neurons with either 5 micrograms/ml pertussis toxin (PTX) or 5 micrograms/ml cholera toxin (CTX) did not significantly affect the suppression of the Ca2+ currents by I-BOP and U-46619. Dialyzing with 1 mM guanosine 5'-O-(3-thiotriphosphate) or 1 mM GDP significantly attenuated the I-BOP or U-46619 action. These results demonstrate that TXA2 agonists inhibit both CgTx- and nimodipine-sensitive Ca2+ currents but not CgTx/nimodipine-insensitive currents in rat hippocampal CA1 neurons via a PTX- and CTX-insensitive G protein-coupled activation of the PKC pathway.

Mechanisms Underlying the Depression of Evoked Fast EPSCs Following In Vitro Ischemia in Rat Hippocampal CA1 Neurons

2001 ◽  
Vol 86 (3) ◽  
pp. 1095-1103 ◽  
Author(s):  
E. Tanaka ◽  
S. Yasumoto ◽  
G. Hattori ◽  
S. Niiyama ◽  
S. Matsuyama ◽  
...  
Keyword(s):  
Brain Slices ◽  
Stratum Radiatum ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ca1 Neurons ◽  
Paired Pulse ◽  
In Vitro Ischemia ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1

The mechanisms underlying the depression of evoked fast excitatory postsynaptic currents (EPSCs) following superfusion with medium deprived of oxygen and glucose (in vitro ischemia) for a 4-min period in hippocampal CA1 neurons were investigated in rat brain slices. The amplitude of evoked fast EPSCs decreased by 85 ± 7% of the control 4 min after the onset of in vitro ischemia. In contrast, the exogenous glutamate-induced inward currents were augmented, while the spontaneous miniature EPSCs obtained in the presence of tetrodotoxin (TTX, 1 μM) did not change in amplitude during in vitro ischemia. In a normoxic medium, a pair of fast EPSCs was elicited by paired-pulse stimulation (40-ms interval), and the amplitude of the second fast EPSC increased to 156 ± 24% of the first EPSC amplitude. The ratio of paired-pulse facilitation (PPF ratio) increased during in vitro ischemia. Pretreatment of the slices with adenosine 1 (A1) receptor antagonist, 8-cyclopenthyltheophiline (8-CPT) antagonized the depression of the fast EPSCs, in a concentration-dependent manner: in the presence of 8-CPT (1–10 μM), the amplitude of the fast EPSCs decreased by only 20% of the control during in vitro ischemia. In addition, 8-CPT antagonized the enhancement of the PPF ratio during in vitro ischemia. A pair of presynaptic volleys and excitatory postsynaptic field potentials (fEPSPs) were extracellularly recorded in a proximal part of the stratum radiatum in the CA1 region. The PPF ratio for the fEPSPs also increased during in vitro ischemia. On the other hand, the amplitudes of the first and second presynaptic volley, which were abolished by TTX (0.5 μM), did not change during in vitro ischemia. The maximal slope of the Ca2+-dependent action potential of the CA3 neurons, which were evoked in the presence of 8-CPT (1 μM), nifedipine (20 μM), TTX (0.5 μM), and tetraethyl ammonium chloride (20 mM), decreased by 12 ± 6% of the control 4 min after the onset of in vitro ischemia. These results suggest that in vitro ischemia depresses the evoked fast EPSCs mainly via the presynaptic A1 receptors, and the remaining 8-CPT–resistant depression of the fast EPSCs is probably due to a direct inhibition of the Ca2+ influx to the axon terminals.

scholarly journals Inactivation of Presenilin in inhibitory neurons results in decreased GABAergic responses and enhanced synaptic plasticity

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sang Hun Lee ◽  
Vadim Y. Bolshakov ◽  
Jie Shen
Keyword(s):  
Synaptic Plasticity ◽  
Calcium Homeostasis ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Ca1 Neurons ◽  
Paired Pulse ◽  
Inhibitory Neurotransmission ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1

AbstractMutations in the Presenilin genes are the major genetic cause of Alzheimer's disease (AD). Presenilin (PS) is highly expressed in the hippocampus, which is particularly vulnerable in AD. Previous studies of PS function in the hippocampus, however, focused exclusively on excitatory neurons. Whether PS regulates inhibitory neuronal function remained unknown. In the current study, we investigate PS function in GABAergic neurons by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from inhibitory neuron-specific PS conditional double knockout (IN-PS cDKO) mice at 2 months of age, before the onset of age-dependent loss of interneurons. We found that the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) is reduced in hippocampal CA1 neurons of IN-PS cDKO mice, whereas the amplitude of sIPSCs is normal. Moreover, the efficacy of inhibitory neurotransmission as assessed with synaptic input/output relations for evoked mono- and di-synaptic IPSCs is markedly lowered in hippocampal CA1 neurons of IN-PS cDKO mice. Consistent with these findings, IN-PS cDKO mice display enhanced paired-pulse facilitation, frequency facilitation and long-term potentiation in the Schaffer collateral-CA1 pathway. Interestingly, depletion of intracellular Ca2+ stores by inhibition of sarcoendoplasmic reticulum Ca2+ ATPase results in a reduction of IPSC amplitude in control hippocampal neurons but not in IN-PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the deficiencies in inhibitory neurotransmission. Furthermore, the amplitude of IPSCs induced by short trains of presynaptic stimulation and paired-pulse ratio are decreased in IN-PS cDKO mice. These findings show that inactivation of PS in interneurons results in decreased GABAergic responses and enhanced synaptic plasticity in the hippocampus, providing additional evidence for the importance of PS in the regulation of synaptic plasticity and calcium homeostasis.

Dose-dependent effects of phencyclidine on hippocampal CA1 neurons

1987 ◽  
Vol 65 (5) ◽  
pp. 842-846 ◽  
Author(s):  
Peter W. Kujtan ◽  
Peter L. Carlen
Keyword(s):  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Low Doses ◽  
Ca1 Neurons ◽  
Firing Rates ◽  
Ca1 Pyramidal Neurons ◽  
Similar Dose ◽  
Hippocampal Ca1 ◽  
High Doses ◽  
Dose Dependent

The dose-dependent effects of phencyclidine were examined in guinea pig hippocampal slices using intracellular and extracellular recordings. Orthodromically evoked population potentials from the CA1 cell body layer were enhanced by low doses (0.2–0.4 μM) and depressed by high doses (0.01–10 mM). Medium doses of the drug (2.0–10.0 μM) showed little effect. Intracellular recordings from CA1 pyramidal neurons gave similar dose-dependent results. Low doses increased spontaneous firing rates and caused silent cells to fire. Medium doses both increased and decreased firing rates, whereas high doses depressed firing rates. Large transient depolarizing shifts were seen in some phencyclidine-treated cells at medium and high doses. Phencyclidine effects took 15–30 min to develop and were only partially reversible after a washout of up to 1 h.

scholarly journals Protective Effect of Apoptosis-Inhibitory Agent, N-Tosyl-l-Phenylalanyl Chloromethyl Ketone against Ischemia-Induced Hippocampal Neuronal Damage

1998 ◽  
Vol 18 (8) ◽  
pp. 819-823 ◽  
Author(s):  
Akira Hara ◽  
Masayuki Niwa ◽  
Masaya Nakashima ◽  
Tomohiko Iwai ◽  
Toshihiko Uematsu ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Hippocampal Neurons ◽  
Therapeutic Strategy ◽  
Neuronal Damage ◽  
Dependent Manner ◽  
Chloromethyl Ketone ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Dose Dependent ◽  
Hippocampal Ca1 Sector

Delayed neuronal death in the gerbil hippocampal CA1 sector occurs 48 to 72 hours after severe forebrain ischemia. DNA fragmentation is observed in the hippocampal CA1 neurons at around that time. We show here that an inhibitor of proteolytic process of apoptosis, N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), protected hippocampal neuronal damage by inhibition of the DNA fragmentation in a dose-dependent manner and that TPCK induced an apoptosis-regulating molecule, Bcl-2 protein, in the surviving neurons. These results suggest the prevention of apoptosis-related DNA fragmentation by TPCK may be an attractive therapeutic strategy for preserving hippocampal neurons from ischemic insult.

Sweet orosensation inducesArcexpression in dorsal hippocampal CA1 neurons in an Experience-dependent manner

Hippocampus ◽  
2015 ◽  
Vol 26 (3) ◽  
pp. 405-413 ◽  
Author(s):  
Yoko O. Henderson ◽  
Rebecca Nalloor ◽  
Almira Vazdarjanova ◽  
Marise B. Parent
Keyword(s):  
Dependent Manner ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Dorsal Hippocampal ◽  
Hippocampal Ca1

Potentiation of NMDA Receptors by Withania somnifera on Hippocampal CA1 Pyramidal Neurons

2013 ◽  
Vol 41 (03) ◽  
pp. 503-513 ◽  
Author(s):  
Janardhan Prasad Bhattarai ◽  
Soo Joung Park ◽  
Seong Kyu Han
Keyword(s):  
Withania Somnifera ◽  
Pyramidal Neurons ◽  
Glycine Receptor ◽  
Patch Clamp Technique ◽  
Pipette Solution ◽  
Ca1 Neurons ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Dose Dependent

In Ayurveda,Withania somnifera (WS) is used as a medicine to maintain mental and physical health as well as to enhance memory. In this study, the methanolic extract of WS(mWS) was tested for its electrical influence on hippocampal CA1 pyramidal neurons using a patch clamp technique. In current clamp mode under a high chloride pipette solution, mWS (400 ng/μl) induced remarkable membrane depolarization (9.75 ± 2.54 mV, n = 6) of CA1 neurons. The mWS-induced depolarization was dose-dependent, reproducible, and persistent in the presence of 0.5 μM tetrodotoxin (TTX, 10.17 ± 0.04 mV, n = 6). In voltage clamp mode (holding potential = -60 mV), mWS induced a dose-dependent non-desensitizing inward current that persisted in the presence of TTX (0.5 μM), suggesting that the response induced by mWS was purely a postsynaptic event. Interestingly, these inward currents were partially blocked by strychnine, a glycine receptor blocker. Further, mWS potentiated the NMDA response in hippocampal CA1 neurons at low concentrations. Overall, these results suggest that there are compounds in WS with possible glycine mimetic activities, which may be potential targets for inducing memory consolidation in hippocampal CA1 neurons.

Ischemic preconditioning protects the hippocampal CA1 neurons by inhibiting synaptic activity in rat

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S300-S300
Author(s):  
Thomas J Sick ◽  
Ami P Raval ◽  
Isabel Saul ◽  
Kunjan R Dave ◽  
Raul Busto ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Synaptic Activity ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1
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