Nimodipine decreases calcium action potentials in rabbit hippocampal CA1 neurons in an age-dependent and concentration-dependent manner

Hippocampus ◽  
1994 ◽  
Vol 4 (1) ◽  
pp. 11-17 ◽  
Author(s):  
James R. Moyer ◽  
John F. Disterhoft
Keyword(s):  
Action Potentials ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Age Dependent ◽  
Calcium Action Potentials

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.

Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner

1992 ◽  
Vol 68 (6) ◽  
pp. 2100-2109 ◽  
Author(s):  
J. R. Moyer ◽  
L. T. Thompson ◽  
J. P. Black ◽  
J. F. Disterhoft
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Input Resistance ◽  
Current Injection ◽  
Spike Frequency ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Nerve Discharge

1. Cellular properties were studied before and after bath application of the dihydropyridine L-type calcium channel antagonist nimodipine in aging and young rabbit hippocampal CA1 pyramidal cells in vitro. Various concentrations of nimodipine, ranging from 10 nM to 10 microM, were tested to investigate age- and concentration-dependent effects on cellular excitability. Drug studies were performed on a population of neurons at similar holding potentials to equate voltage-dependent effects. The properties studied under current-clamp conditions included steady-state current-voltage relations (I-V), the amplitude and integrated area of the postburst afterhyperpolarization (AHP), accommodation to a prolonged depolarizing current pulse (spike frequency adaptation), and single action-potential waveform characteristics following synaptic activation. 2. Numerous aging-related differences in cellular properties were noted. Aging hippocampal CA1 neurons exhibited significantly larger postburst AHPs (both the amplitude and the integrated area were enhanced). Aging CA1 neurons also exhibited more hyperpolarized resting membrane potentials with a concomitant decrease in input resistance. When cells were grouped to equate resting potentials, no differences in input resistance were noted, but the AHPs were still significantly larger in aging neurons. Aging CA1 neurons also fired fewer action potentials during a prolonged depolarizing current injection than young CA1 neurons. 3. Nimodipine decreased both the peak amplitude and the integrated area of the AHP in an age- and concentration-dependent manner. At concentrations as low as 100 nM, nimodipine significantly reduced the AHP in aging CA1 neurons. In young CA1 neurons, nimodipine decreased the AHP only at 10 microM. No effects on input resistance or action-potential characteristics were seen. 4. Nimodipine increased excitability in an age- and concentration-dependent manner by decreasing spike frequency accommodation (increasing the number of action potentials during prolonged depolarizing current injection). In aging CA1 neurons, this effect was significant at concentrations as low as 10 nM. In young CA1 neurons, nimodipine decreased accommodation only at higher concentrations (> or = 1.0 microM). 5. We conclude that aging CA1 neurons were less excitable than young neurons. In aging hippocampus, nimodipine restores excitability, as measured by size of the AHP and degree of accommodation, to levels closely resembling those of young adult CA1 neurons. These actions of nimodipine on aging CA1 hippocampal neurons may partly underlie the drug's notable ability to improve associative learning in aging rabbits and other mammals. Reversal of inhibitory postsynaptic potentials (IPSPs) by chloride ion and/or current injections into six motoneurons revealed the presence of inhibition during the period between phrenic bursts during fictive vomiting and also during the final phase of expulsion when phrenic discharge ceased by abdominal discharge continued. 3. Fictive coughing, evoked by repetitive electrical stimulation of superior laryngeal nerve afferents, was characterized by a large phrenic discharge followed immediately by a large abdominal nerve discharge. During fictive coughing, phrenic motoneurons retained their ramplike depolarizations throughout phrenic discharge; however, the amplitude of depolarization was greater than during inspiration. During the subsequent abdominal nerve discharge, the phrenic membrane potential usually underwent an initial rapid, transient hyperpolarization followed by a gradual repolarization associated with increased synaptic noise.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Libin Zhou ◽  
Joseph Flores ◽  
Anastasia Noël ◽  
Olivier Beauchet ◽  
P. Jesper Sjöström ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cognitive Deficits ◽  
Synaptic Function ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Age Dependent ◽  
Caspase 6

AbstractActivated Caspase-6 (Casp6) is associated with age-dependent cognitive impairment and Alzheimer disease (AD). Mice expressing human Caspase-6 in hippocampal CA1 neurons develop age-dependent cognitive deficits, neurodegeneration and neuroinflammation. This study assessed if methylene blue (MB), a phenothiazine that inhibits caspases, alters Caspase-6-induced neurodegeneration and cognitive impairment in mice. Aged cognitively impaired Casp6-overexpressing mice were treated with methylene blue in drinking water for 1 month. Methylene blue treatment did not alter Caspase-6 levels, assessed by RT-PCR, western blot and immunohistochemistry, but inhibited fluorescently-labelled Caspase-6 activity in acute brain slice intact neurons. Methylene blue treatment rescued Caspase-6-induced episodic and spatial memory deficits measured by novel object recognition and Barnes maze, respectively. Methylene blue improved synaptic function of hippocampal CA1 neurons since theta-burst long-term potentiation (LTP), measured by field excitatory postsynaptic potentials (fEPSPs) in acute brain slices, was successfully induced in the Schaffer collateral-CA1 pathway in methylene blue-treated, but not in vehicle-treated, Caspase-6 mice. Increased neuroinflammation, measured by ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia numbers and subtypes, and glial fibrillary acidic protein (GFAP)-positive astrocytes, were decreased by methylene blue treatment. Therefore, methylene blue reverses Caspase-6-induced cognitive deficits by inhibiting Caspase-6, and Caspase-6-mediated neurodegeneration and neuroinflammation. Our results indicate that Caspase-6-mediated damage is reversible months after the onset of cognitive deficits and suggest that methylene blue could benefit Alzheimer disease patients by reversing Caspase-6-mediated cognitive decline.

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

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.

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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