Somatostatin Increases a Voltage-Insensitive K+ Conductance in Rat CA1 Hippocampal Neurons

1998 ◽  
Vol 79 (3) ◽  
pp. 1230-1238 ◽  
Author(s):  
Paul Schweitzer ◽  
Samuel G. Madamba ◽  
George R. Siggins
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Specific Inhibitor ◽  
Outward Current ◽  
Resting Potential ◽  
Resting Membrane Potential ◽  
High Concentration ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Schweitzer, Paul, Samuel G. Madamba, and George R. Siggins. Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons. J. Neurophysiol. 79: 1230–1238, 1998. Somatostatin (SST) is a neuropeptide involved in several central processes. In hippocampus, SST hyperpolarizes CA1 pyramidal neurons and augments the K+ M current ( I M). However, the limited involvement of I M at resting potential in these cells suggests that the peptide also may modulate another channel to hyperpolarize hippocampal pyramidal neurons (HPNs). We studied the effect of SST on noninactivating conductances of rat CA1 HPNs in a slice preparation. Using MK886, a specific inhibitor of the enzymatic pathway that leads to the augmentation of I M by SST, we have uncovered and characterized a second conductance activated by the peptide. SST did not affect I M when applied with MK886 or the amplitudes of the slow Ca2+-dependent K+ afterhyperpolarization-current and the cationic Q current but still caused an outward current, indicating that SST acts upon another conductance. In the presence of MK886, SST elicited an outward current that reversed around −100 mV and that displayed a linear current-voltage relationship. Reversal potentials obtained in different external K+ concentrations are consistent with a conductance carried solely by K+ ions. The slope of the current-voltage relationship increased proportionately with the extracellular K+ concentration and remained linear. This suggests that SST opens a voltage-insensitive leak current ( I K(L)) in HPNs not an inwardly rectifying K+ current as reported in other neuron types. A low concentration of extracellular Ba2+ (150 μM) only slightly decreased the SST-induced effect in a voltage-independent manner, whereas a high concentration of Ba2+ (2 mM) completely blocked it. Extracellular Cs+ (2 mM) did not affect the outward SST current but inhibited the inward component. We conclude that SST inhibits HPNs by activating two different K+ conductances: the voltage-insensitive I K(L) and the voltage-dependent I M. The hyperpolarizing effect of SST at resting membrane potential appears to be mainly carried by I K(L), whereas I M dominates at slightly depolarized potentials.

scholarly journals Ionic Basis of Membrane Potential and of Acetylcholine-evduced Currents in the Cell Body of the Cockroach Fast Coxal Depressor Motor Neurone

1990 ◽  
Vol 151 (1) ◽  
pp. 21-39 ◽  
Author(s):  
JONATHAN A. DAVID ◽  
DAVID B. SATTELLE
Keyword(s):  
Cell Body ◽  
Outward Current ◽  
Motor Neurone ◽  
Resting Potential ◽  
Inward Current ◽  
Current Voltage ◽  
Low K ◽  
Current Voltage Relationship ◽  
Ionic Basis ◽  
Voltage Relationship

The ionic basis of the resting potential and of the response to acetylcholine (ACh) has been investigated in the cell body membrane of the fast coxal depressor motor neurone in the metathoracic ganglion of the cockroach Periplaneta americana. By means of ion-sensitive microelectrodes, intracellular concentrations of three ion species were estimated (mmoll−1): [K+]i, 1443; [Na+]i, 9±1; [Cl−], 7±1. The resting potential of continuously superfused cells was −75.6±1.9mV at 22° C. A change in resting potential of 42.0±2.5mV accompanied a decade change in [K+]o. Experiments with (10−4moll−1) ouabain, Na+ injection, low temperature (10°C) and non-superfused cells indicated the presence of an electrogenic sodium pump. Under current-clamp, the cell body membrane was depolarized by sequentially applied, ionophoretic pulses (500ms duration) of ACh. Under voltage-clamp, such doses of ACh resulted in an inward current which was abolished in low-Na+ saline. Ion-sensitive electrodes revealed an increase in [Na+]i but no change in [Cl−1]j in response to externally applied ACh. The ACh-induced current-voltage relationship was shifted in a negative direction by low-K+ saline. The AChinduced inward current was usually followed by a delayed outward current which reversed at Ek. Low-K+ saline had the same effect on this outward component as depolarizing the membrane. This suggests that the outward current component is carried by K+. The ACh-induced inward current and the delayed outward current were potentiated either when [Ca2+]i was lowered by injecting the calcium chelator BAPTA or by exposure of the cell to low-Ca2+ saline. High-Ca2+ saline reduced the inward component of the response and produced a negative shift in the AChinduced current-voltage relationship. The amplitude of the delayed outward

Methods for intracellular recording from hippocampal brain slices under high helium pressure

1991 ◽  
Vol 71 (1) ◽  
pp. 365-371 ◽  
Author(s):  
A. P. Southan ◽  
K. T. Wann
Keyword(s):  
Intracellular Recording ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Pressure Chamber ◽  
Resting Membrane Potential ◽  
Helium Pressure ◽  
Remote Manipulation ◽  
Current Voltage ◽  
Chamber Temperature ◽  
Current Voltage Relationship

A method for intracellular recording from rat hippocampal brain slices under helium pressure is described. The preparation is mounted on a horizontal mobile platform that is rolled into the pressure chamber and can be viewed at pressure. Remote manipulation of the glass microelectrodes is achieved by a high-resolution electrically driven commercially available system. The slice is superfused continuously from a closed system within the chamber. Temperature is maintained at 37 degrees C and PO2 at 0.5 atm within the pressure chamber. A pressure of 200 ATA can be obtained, although thus far recordings have been made up to only 130 ATA. The experiments demand that a number of sample recordings be made from the same slice at both ambient and high pressure, and tests have proved that, although difficult, this can be achieved. The resting membrane potential, the current-voltage relationship, and the action potential responses to short (8 ms), medium (80 ms), and long (800 ms) depolarizing current pulses have all been measured in CA1 pyramidal neurons.

scholarly journals Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels

2020 ◽  
Vol 21 (24) ◽  
pp. 9639
Author(s):  
Yeonju Bae ◽  
Jae Hyouk Choi ◽  
Kanghyun Ryoo ◽  
Ajung Kim ◽  
Osung Kwon ◽  
...  
Keyword(s):  
Brain Slices ◽  
Specific Inhibitor ◽  
Excitable Cells ◽  
Cultured Astrocytes ◽  
Current Voltage ◽  
Molecular Machinery ◽  
Hippocampal Astrocytes ◽  
Current Voltage Relationship ◽  
The Brain ◽  
Voltage Relationship

Astrocytes, the most abundant cell type in the brain, are non-excitable cells and play critical roles in brain function. Mature astrocytes typically exhibit a linear current–voltage relationship termed passive conductance, which is believed to enable astrocytes to maintain potassium homeostasis in the brain. We previously demonstrated that TWIK-1/TREK-1 heterodimeric channels mainly contribute to astrocytic passive conductance. However, the molecular identity of astrocytic passive conductance is still controversial and needs to be elucidated. Here, we report that spadin, an inhibitor of TREK-1, can dramatically reduce astrocytic passive conductance in brain slices. A series of gene silencing experiments demonstrated that spadin-sensitive currents are mediated by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Our study clearly showed that TWIK-1/TREK-1-heterodimeric channels can act as the main molecular machinery of astrocytic passive conductance, and suggested that spadin can be used as a specific inhibitor to control astrocytic passive conductance.

scholarly journals Contributions of space-clamp errors to apparent time-dependent loss of Mg2+ block induced by NMDA

2017 ◽  
Vol 118 (1) ◽  
pp. 532-543
Author(s):  
Min-Yu Sun ◽  
Mariangela Chisari ◽  
Lawrence N. Eisenman ◽  
Charles F. Zorumski ◽  
Steven J. Mennerick
Keyword(s):  
Voltage Clamp ◽  
Hippocampal Neurons ◽  
Network Activity ◽  
Negative Slope ◽  
Secondary Currents ◽  
Current Voltage ◽  
Nmda Current ◽  
Current Voltage Relationship ◽  
Voltage Relationship ◽  
Juvenile Mouse

N-methyl-d-aspartate receptors (NMDARs) govern synaptic plasticity, development, and neuronal response to insult. Prolonged activation of NMDARs such as during an insult may activate secondary currents or modulate Mg2+ sensitivity, but the conditions under which these occur are not fully defined. We reexamined the effect of prolonged NMDAR activation in juvenile mouse hippocampal slices. NMDA (10 μM) elicited current with the expected negative-slope conductance in the presence of 1.2 mM Mg2+. However, several minutes of continued NMDA exposure elicited additional inward current at −70 mV. A higher concentration of NMDA (100 µM) elicited the current more rapidly. The additional current was not dependent on Ca2+, network activity, or metabotropic NMDAR function and did not persist on agonist removal. Voltage ramps revealed no alteration of either reversal potential or NMDA-elicited conductance between −30 mV and +50 mV. The result was a more linear NMDA current-voltage relationship. The current linearization was also induced in interneurons and in mature dentate granule neurons but not immature dentate granule cells, dissociated cultured hippocampal neurons, or nucleated patches excised from CA1 pyramidal neurons. Comparative simulations of NMDA application to a CA1 pyramidal neuron and to a cultured neuron revealed that linearization can be explained by space-clamp errors arising from gradual recruitment of distal dendritic NMDARs. We conclude that persistent secondary currents do not strongly contribute to NMDAR responses in juvenile mouse hippocampus and careful discernment is needed to exclude contributions of clamp artifacts to apparent secondary currents. NEW & NOTEWORTHY We report that upon sustained activation of NMDARs in juvenile mouse hippocampal neurons there is apparent loss of Mg2+ block at negative membrane potentials. However, the phenomenon is explained by loss of dendritic voltage clamp, leading to a linear current-voltage relationship. Our results give a specific example of how spatial voltage errors in voltage-clamp recordings can readily be misinterpreted as biological modulation.

1S,3R-ACPD Induces a Region of Negative Slope Conductance in the Steady-State Current-Voltage Relationship of Hippocampal Pyramidal Cells

1997 ◽  
Vol 77 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Anita Lüthi ◽  
Beat H. Gähwiler ◽  
Urs Gerber
Keyword(s):  
Steady State ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Negative Slope ◽  
Inward Current ◽  
Current Voltage ◽  
Steady State Current ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Lüthi, Anita, Beat H. Gähwiler, and Urs Gerber. 1 S,3 R-ACPD induces a region of negative slope conductance in the steady-state current-voltage relationship of hippocampal pyramidal cells. J. Neurophysiol. 77: 221–228, 1997. Synaptic responses mediated by metabotropic glutamate receptors (mGluRs) display a marked voltage-dependent increase in amplitude when neurons are moderately depolarized beyond membrane potential. We have investigated the basis for this apparent nonlinear behavior by activatingmGluRs with 1 S,3 R-1-aminocyclopentane-1,3-dicarboxylate(1 S,3 R-ACPD; 10 μM) in CA3 pyramidal cells from rat hippocampal slice cultures with the use of the single-electrode voltage-clamp technique. Under control conditions, cells depolarized from resting potential by 10–20 mV responded with delayed outwardly rectifying currents due to activation of voltage- and Ca2+-dependent K+ conductances. In contrast, in the continuous presence of 1 S,3 R-ACPD, small depolarizations (10–20 mV) induced a delayed inward current. The steady-state current-voltage relationship for this response displayed a region of negative slope conductance at potentials between −55 and −40 mV. The reversal potential of the corresponding 1 S,3 R-ACPD-sensitive tail currents (−93.0 ± 2.2 mV, mean ± SE) was close to the potassium reversal potential, consistent with an mGluR-mediated suppression of K+ current. When external K+ concentration was increased to 8 mM, there was a positive shift in reversal potential to −76.9 ± 5.1 mV. The depolarization-induced inward current in the presence of 1 S,3 R-ACPD was blocked by Ba2+ (1 mM). The response was not dependent on changes in intracellular Ca2+ concentration and was insensitive to bath-applied Cs+ (1 mM), ruling out a contribution of Ca2+-dependent currents or the inward rectifier I Q. Furthermore, the effect of 1 S,3 R-ACPD was not mimicked by inhibiting afterhyperpolarizing current and M current with low-Ca2+ saline (0.5 mM Ca2+, 10 mM Mg2+) containing 10 mM tetraethylammonium chloride. A comparison of the responses induced by 1 S,3 R-ACPD and N-methyl-d-aspartate showed that both induce an inward current with small depolarizations from resting potential but with different kinetics and Mg2+ sensitivity. These results indicate that the suppression of K+ currents in response to activation of mGluRs is markedly voltage dependent, increasing at depolarized potentials and decreasing at hyperpolarized potentials. The negative slope conductance at membrane voltages positive to resting potential may underlie the amplification of mGluR-mediated responses when the membrane potential approaches action potential threshold.

scholarly journals Acetylcholine-induced current in perfused rat myoballs.

1980 ◽  
Vol 75 (3) ◽  
pp. 297-321 ◽  
Author(s):  
R Horn ◽  
M S Brodwick
Keyword(s):  
Membrane Potential ◽  
Time Course ◽  
Striated Muscle ◽  
Membrane Surface ◽  
Reversal Potential ◽  
Neonatal Rat ◽  
Resting Potential ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Spherical "myoballs" were grown under tissue culture conditions from striated muscle of neonatal rat thighs. The myoballs were examined electrophysiologically with a suction pipette which was used to pass current and perfuse internally. A microelectrode was used to record membrane potential. Experiments were performed with approximately symmetrical (intracellular and extracellular) sodium aspartate solutions. The resting potential, acetylcholine (ACh) reversal potential, and sodium channel reversal potential were all approximately 0 mV. ACh-induced currents were examined by use of both voltage jumps and voltage ramps in the presence of iontophoretically applied agonist. The voltage-jump relaxations had a single exponential time-course. The time constant, tau, was exponentially related to membrane potential, increasing e-fold for 81 mV hyperpolarization. The equilibrium current-voltage relationship was also approximately exponential, from -120 to +81 mV, increasing e-fold for 104 mV hyperpolarization. The data are consistent with a first-order gating process in which the channel opening rate constant is slightly voltage dependent. The instantaneous current-voltage relationship was sublinear in the hyperpolarizing direction. Several models are discussed which can account for the nonlinearity. Evidence is presented that the "selectivity filter" for the ACh channel is located near the intracellular membrane surface.

Injection of RNA from carp retina induces the formation of a membrane potassium channel in Xenopus oocytes

1991 ◽  
Vol 6 (1) ◽  
pp. 69-74
Author(s):  
Lawrence H. Pinto ◽  
Akimichi Kaneko
Keyword(s):  
Xenopus Oocytes ◽  
Reversal Potential ◽  
Outward Current ◽  
Fold Increase ◽  
Bipolar Cells ◽  
Total Rna ◽  
Outward Currents ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

AbstractTotal RNA was purified from freshly isolated retinas of adult carp and injected into oocytes of Xenopus laevis (stage 5–6). Two to six days after injection, depolarizing voltage-clamp steps evoked a slowly activated outward currents as large as 3 μA. This current inactivated slowly with a single time constant (τ= 3.1 ± 0.24 S.E.M., for Vm= +30 mV). The current was inhibited by tetraethylammonium (3.8 mM for half-maximal inhibition). In the presence of Co2+ (1 mM) or barium methanesulfonate (40 mM), the current-voltage relationship shifted to slightly more depolarized values (5–10 mV); the maximal value of the current that was sensitive to Co2+ or Ba2+ treatments was only a small fraction (about 10%) of the TEA-sensitive current, and its current-voltage relationship was similar to that for uninjected oocytes. The reversal potential of the membrane current was studied with [K+]0 of 1–77 mM. For [K+]0 > 20 mM, the reversal potential changed with a slope of 63 mV (±;2 mV S.E.M.) per 10-fold change in [K+]0. The conductance was induced half-maximally at 17 mV (±;0.9 mV s.e.m.). The depolarization required for an e−fold increase in conductance was 13 mV (±;0.6 mV s.e.m.). From these results, we conclude that the injection of total RNA from carp retinas induces the formation of a membrane K+ channel in Xenopus oocytes. The channel formed has many of properties reported for the maintained outward current of goldfish horizontal and bipolar cells.

Action of Lindane on the Current-Voltage Relationship in the Plasma Membrane of Elodea under Passive Conditions

1979 ◽  
Vol 34 (11) ◽  
pp. 1072-1074 ◽  
Author(s):  
Kurt Schefczik ◽  
Wilhelm Simonis
Keyword(s):  
Plasma Membrane ◽  
Current Flow ◽  
Single Cells ◽  
Outward Current ◽  
Membrane Resistance ◽  
Strong Nonlinearity ◽  
Elodea Densa ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Abstract Side effects of the chlorinated hydrocarbon insecticide Lindane on the plasma membrane of the submerged macrophytic fresh-water plant Elodea densa were studied. Single glass microelectrodes were inserted into single cells and membrane potential, membrane resistance and electrode resistance were recorded using a new designed electrophysiological monitoring system (“ELM 2”). The current-voltage relationship in the plasma membrane of Elodea cells under passive conditions is nearly linear for relaxing current pulses up to 10-8 amperes. Lindane treatment, produced first (3.5 hours) a strong nonlinearity in current-voltage relationship with increased membrane resistance for inward current flow, and later (24.5 hours) an increased membrane resistance both for inward and outward current flow. It is discussed that the earlier reported lowering of the potassium selectivity in the plasma membrane of Elodea after Lindane treatment will be the reason for the alterations of current-voltage relationship.

scholarly journals Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Shigetomo Suyama ◽  
Alexandra Ralevski ◽  
Zhong-Wu Liu ◽  
Marcelo O Dietrich ◽  
Toshihiko Yada ◽  
...  
Keyword(s):  
Food Deprivation ◽  
High Fat Diet ◽  
Receptor Complex ◽  
High Fat ◽  
Fasted State ◽  
Linear Current ◽  
Current Voltage ◽  
Relationship Of ◽  
Current Voltage Relationship ◽  
Voltage Relationship

POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state. Ten days of high-fat diet exposure, which was accompanied by elevated leptin levels and increased POMC neuronal activity, resulted in increased expression of Cp-AMPARs on POMC neurons. Altogether, our results show that entry of calcium via Cp-AMPARs is inherent to activation of POMC neurons, which may underlie a vulnerability of these neurons to calcium overload while activated in a sustained manner during over-nutrition.

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