Modulation of voltage-dependent sodium channels by the δ-agonist SNC80 in acutely isolated rat hippocampal neurons

2004 ◽  
Vol 47 (7) ◽  
pp. 1102-1112 ◽  
Author(s):  
Christina Remy ◽  
Stefan Remy ◽  
Heinz Beck ◽  
Dieter Swandulla ◽  
Michael Hans
Keyword(s):  
Sodium Channels ◽  
Hippocampal Neurons ◽  
Voltage Dependent ◽  
Isolated Rat

Late Sodium Channel Openings Underlying Epileptiform Activity Are Preferentially Diminished by the Anticonvulsant Phenytoin

1997 ◽  
Vol 77 (6) ◽  
pp. 3021-3034 ◽  
Author(s):  
Michael M. Segal ◽  
Andrea F. Douglas
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Hippocampal Neurons ◽  
Sodium Current ◽  
Epileptiform Activity ◽  
Normal Function ◽  
Anticonvulsant Effect ◽  
Persistent Sodium Current ◽  
Pharmacological Mechanism ◽  
Voltage Dependent

Segal, Michael M. and Andrea F. Douglas. Late sodium channel openings underlying epileptiform activity are preferentially diminished by the anticonvulsant phenytoin. J. Neurophysiol. 77: 3021–3034, 1997. Late openings of sodium channels were observed in outside-out patch recordings from hippocampal neurons in culture. In previous studies of such neurons, a persistent sodium current appeared to underlie the ictal epileptiform activity. All the channel currents were blocked by tetrodotoxin. In addition to the transient openings of sodium channels making up the peak sodium current, there were two types of late channel openings: brief late and burst openings. These late channel openings occurred throughout voltage pulses that lasted 750 ms, producing a persistent sodium current. At −30 mV, this current was 0.4% of the peak current. The late channel openings occurred throughout the physiological range of trans-membrane voltages. The anticonvulsant phenytoin reduced the late channel openings more than the peak currents. The effect on the persistent current was greatest at more depolarized voltages, whereas the effect on peak currents was not substantially voltage dependent. In the presence of 60 μM phenytoin, peak sodium currents at −30 mV were 40–41% of control, as calculated using different methods of analysis. Late currents were 22–24% of control. Phenytoin primarily decreased the number of channel openings, with less effect on the duration of channel openings and no effect on open channel current. This set of findings is consistent with models in which phenytoin binds to the inactivated state of the channel. The preferential effect of phenytoin on the persistent sodium current suggests that an important pharmacological mechanism for a sodium channel anticonvulsant is to reduce late openings of sodium channels, rather than reducing all sodium channel openings. We hypothesize that pharmacological interventions that are most selective in reducing late openings of sodium channels, while leaving early channel openings relatively intact, will be those that produce an anticonvulsant effect while interfering minimally with normal function.

Blockade of the voltage-dependent sodium current in isolated rat hippocampal neurons by tetrodotoxin and lidocaine

1989 ◽  
Vol 484 (1-2) ◽  
pp. 348-351 ◽  
Author(s):  
Makoto Kaneda ◽  
Yasuo Oyama ◽  
Yoshimi Ikemoto ◽  
Norio Akaike
Keyword(s):  
Hippocampal Neurons ◽  
Sodium Current ◽  
Voltage Dependent ◽  
Isolated Rat

4-aminopyridine derivatives: A family of novel modulators of voltage-dependent sodium channels

1998 ◽  
Vol 44 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Lei Tang ◽  
Francis P. Huger ◽  
Joseph T. Klein ◽  
Larry Davis ◽  
Lawrence L. Martin ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Voltage Dependent

Altered Regulation of Potassium and Calcium Channels by GABAB and Adenosine Receptors in Hippocampal Neurons From Mice Lacking Gαo

2000 ◽  
Vol 83 (2) ◽  
pp. 1010-1018 ◽  
Author(s):  
Gabriela J. Greif ◽  
Deborah L. Sodickson ◽  
Bruce P. Bean ◽  
Eva J. Neer ◽  
Ulrike Mende
Keyword(s):  
Time Constant ◽  
Hippocampal Neurons ◽  
Ionic Currents ◽  
Absolute Requirement ◽  
Voltage Dependent ◽  
Hippocampal Ca3 ◽  
Ca3 Neurons ◽  
Inwardly Rectifying ◽  
G Protein Coupled

To examine the role of Go in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of Gαo. In CA3 neurons from Gαo −/− mice, 2-chloro-adenosine and the GABAB-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited voltage-dependent Ca2+ currents just as effectively as in Gαo +/+ littermates. However, the kinetics of transmitter action were dramatically altered in Gαo −/− mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from Gαo −/− mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from Gαo +/+ mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca2+ currents and K+currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking Gαo, some inhibition of Ca2+ currents by baclofen remained after NEM treatment, whereas baclofen activation of K+ currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca2+ and K+ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for Gαo. However, modulation is changed in the absence of Gαo in having much slower recovery kinetics. A likely possibility is that the very abundant Gαo is normally used but, when absent, can readily be replaced by G proteins with different properties.

Up-regulation of functional voltage-dependent sodium channels by cyclic AMP-dependent protein kinase in adrenal medulla

1996 ◽  
Vol 709 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Tomoaki Yuhi ◽  
Akihiko Wada ◽  
Ryuichi Yamamoto ◽  
Toshihiko Yanagita ◽  
Hiromi Niina ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Sodium Channels ◽  
Adrenal Medulla ◽  
Dependent Protein Kinase ◽  
Voltage Dependent ◽  
Dependent Protein

Differential Oxidative Modulation of Voltage-Dependent K+ Currents in Rat Hippocampal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2990-2995 ◽  
Author(s):  
Wolfgang Müller ◽  
Katrin Bittner
Keyword(s):  
Hydrogen Peroxide ◽  
Hippocampal Neurons ◽  
Immune Defense ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Currents ◽  
Stimulation Of

Oxidative stress is enhanced by [Ca2+]i-dependent stimulation of phospholipases and mitochondria and has been implicated in immune defense, ischemia, and excitotoxicity. Using whole cell recording from hippocampal neurons, we show that arachidonic acid (AA) and hydrogen peroxide (H2O2) both reduce the transient K+ current I A by −54 and −68%, respectively, and shift steady-state inactivation by −10 and −15 mV, respectively. While AA was effective at an extracellular concentration of 1 μM and an intracellular concentration of 1 pM, extracellular H2O2 was equally effective only at a concentration >800 μM (0.0027%). In contrast to AA, H2O2 decreased the slope of activation and increased the slope of inactivation of I A and reduced the sustained delayed rectifier current I K(V) by 22% and shifted its activation by −9 mV. Intracellular application of the antioxidant glutathione (GSH, 2–5 mM) blocked all effects of AA and the reduction of I A by H2O2. In contrast, intracellular GSH enhanced reduction of I K(V) by H2O2. Decrease of the slope of activation and increase of the slope of inactivation of I A by hydrogen peroxide was blocked and reversed to a decrease, respectively, by intracellular application of GSH. Intracellular GSH did not prevent H2O2 to shift inactivation and activation of I A and activation of I K(V) to more negative potentials. We conclude, that AA and H2O2modulate voltage-activated K currents differentially by oxidation of GSH accessible intracellular and GSH inaccessible extracellular K+-channel domains, thereby presumably affecting neuronal information processing and oxidative damage.

Voltage-dependent modulation of GABAA receptor channel desensitization in rat hippocampal neurons

1994 ◽  
Vol 71 (6) ◽  
pp. 2151-2160 ◽  
Author(s):  
K. W. Yoon
Keyword(s):  
Membrane Potential ◽  
Hippocampal Neurons ◽  
Membrane Conductance ◽  
Cell Voltage ◽  
Chloride Conductance ◽  
Membrane Voltage ◽  
Hippocampal Cell Culture ◽  
Voltage Dependent ◽  
Agonist Concentration ◽  
Rate Of Recovery

1. The mechanism of the time-dependent decline in gamma-amino-butyric acid (GABA)-induced chloride conductance, referred to as desensitization, was studied in dissociated rat hippocampal cell culture with the use of a whole-cell voltage-clamp recording. 2. In most cells the gradual decline of membrane conductance was dependent simultaneously on the agonist concentration and membrane voltage. Even in the continued presence of GABA, desensitization could be prevented by holding the membrane potential > 0 mV in a near symmetrical chloride gradient across the cell membrane. 3. The “recovery” from desensitization occurred after removal of the agonist with a time constant of approximately 35 s. The rate of recovery from desensitization was independent of membrane voltage. 4. When the membrane potential was jumped from a negative to a positive membrane potential during steady state of desensitization, the GABA-induced chloride conductance gradually “relaxed” to the undesensitized state. This phenomenon of gradual increase in chloride conductance or “reactivation” from desensitization was both voltage and agonist dependent. 5. The process of recovery of the GABA ionophore from the desensitized state is distinct from the process of reactivation, which is dependent both on the voltage and agonist. 6. These observations suggest that the ligand-bound GABA receptor has two alternate states, i.e., permissive (activated) and desensitized. The rates of transition between these two states are voltage dependent.

scholarly journals Characteristic of the vasorlaxant action of the talatisamine alkaloid and its derivatives

2021 ◽  
Vol 4 (2) ◽  
pp. 01-05
Author(s):  
Mirzayeva Yu.T.
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Channel Blocker ◽  
Aortic Ring ◽  
Diterpenoid Alkaloids ◽  
Relaxant Effect ◽  
Ring Contraction ◽  
Voltage Dependent ◽  
Ca2 Channels ◽  
Isolated Rat

The aim of our research is to study the effect relaxant action of diterpenoid alkaloids talatisamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine was studied using isolated rat aortic rings. Alkaloids significantly and dose-dependently inhibited contraction of the aortic rings caused by high KCl content. At the same time, under these conditions, alkaloids significantly reduced Ca2+-induced contraction of the aortic rings. The relaxing effects of alkaloids are significantly suppressed by verapamil, a potent potentiometer-dependent Ca2+ channel blocker. The alkaloids also significantly reduced norepinephrine-induced aortic ring contraction in normal as well as Ca2+ free Krebs solutions. The data obtained indicate that talatisamine, 14-benzoylthalatisamine and 14-O-acetylthalatisamine exhibit a pronounced relaxant effect in almost the same way in the case of contraction induced by a high content of KCl and norepinephrine. The mechanism of the relaxant action of alkaloids is probably complex and may include suppression of Ca2+influx through voltage-dependent and receptor-driven Ca2+ channels, as well as inhibition of Ca2+transport in the sarcoplasmic reticulum.

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