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 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

scholarly journals The Ventral Photoreceptor Cells of Limulus

1969 ◽  
Vol 54 (3) ◽  
pp. 331-351 ◽  
Author(s):  
Ronald Millecchia ◽  
Alexander Mauro
Keyword(s):  
Steady State ◽  
Voltage Clamp ◽  
Dark Current ◽  
Time Course ◽  
Reversal Potential ◽  
Negative Slope ◽  
Induced Current ◽  
Current Voltage ◽  
Steady State Current ◽  
Current Voltage Relation

In the dark, the ventral photoreceptor of Limulus exhibits time-variant currents under voltage-clamp conditions; that is, if the membrane potential of the cell is clamped to a depolarized value there is an initial large outward current which slowly declines to a steady level. The current-voltage relation of the cell in the dark is nonlinear. The only ion tested which has any effect on the current-voltage relation is potassium; high potassium shifts the reversal potential towards zero and introduces a negative slope-conductance region. When the cell is illuminated under voltage-clamp conditions, an additional current, the light-induced current, flows across the cell membrane. The time course of this current mimics the time course of the light response (receptor potential) in the unclamped cell; namely, an initial transient phase is followed by a steady-state phase. The amplitude of the peak transient current can be as large as 60 times the amplitude of the steady-state current, while in the unclamped cell the amplitude of the peak transient voltage never exceeds 4 times the amplitude of the steady-state voltage. The current-voltage relations of the additional light-induced current obtained for different instants of time are also nonlinear, but differ from the current-voltage relations of the dark current. The ions tested which have the greatest effect on the light-induced current are sodium and calcium; low sodium decreases the current, while low calcium increases the current. The data strongly support the hypothesis that two systems of electric current exist in the membrane. Thus the total ionic current which flows in the membrane is accounted for as the sum of a dark current and a light-induced current.

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.

Citrate decreases contraction and Ca current in cardiac muscle independent of its buffering action

1991 ◽  
Vol 260 (5) ◽  
pp. C900-C909 ◽  
Author(s):  
D. M. Bers ◽  
L. V. Hryshko ◽  
S. M. Harrison ◽  
D. D. Dawson
Keyword(s):  
Cardiac Muscle ◽  
Dipicolinic Acid ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Nitrilotriacetic Acid ◽  
Ca Current ◽  
Current Voltage ◽  
Protonated Forms ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Extracellular Ca (Cao) depletions that occur during cardiac muscle contractions are indicative of net Ca entry. Buffering Cao concentration ([Ca]o) with citrate can limit the magnitude of these Cao depletions [e.g., Shattock and Bers. Am. J. Physiol. 256 (Cell Physiol. 25): C813-C822, 1989] which theoretically would allow more Ca entry and consequently greater force at the same free [Ca]o. However, Shimoni and Ginsburg [Am. J. Physiol. 252 (Cell Physiol. 21): C248-C252, 1987] have shown that citrate inhibits cardiac contractions and suggested that this was due to its Ca-buffering action (i.e., dissipating a local elevation of [Ca] at the outer sarcolemmal surface and thereby decreasing Ca influx). To examine the effects of Ca buffering per se, we compared the effects of four low-affinity Ca buffers [citrate, nitrilotriacetic acid (NTA), dipicolinic acid (DPA), and acetamidoiminodiacetic acid (ADA)] on several cardiac preparations. In Mg-free medium with 2 mM free Ca (measured using murexide), citrate, DPA, and ADA (10 mM) decreased the force of twitch contractions in rabbit ventricle to 76 +/- 2, 60 +/- 2, and 85 +/- 2%, respectively, but 10 mM NTA increased force slightly to 105 +/- 2%. No simple correlation was observed between the Ca affinity of the buffer and its effect on tension. These effects were not due to changes in sarcoplasmic reticulum (SR) Ca loading because rapid cooling contractures were not affected and similar results were observed in the presence of caffeine or ryanodine. The depressant effects of citrate and ADA on tension were greater at pH 5.5-6 and ADA had no effect at pH 8.5. Thus the depressant effect is stronger with more protonated forms of citrate and ADA, which are also poorer Ca buffers. Citrate (but not NTA) decreased Ca current in whole cell voltage clamp and shifted the current-voltage relationship and reversal potential to more negative potentials. Citrate decreased Ca current more effectively at higher citrate and lower Ca concentrations. We conclude that citrate (and some other weak Ca buffers) may directly decrease Ca current and contraction in a manner independent of Ca buffering ability.

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.

TMEM16F is a component of a Ca2+-activated Cl− channel but not a volume-sensitive outwardly rectifying Cl− channel

2013 ◽  
Vol 304 (8) ◽  
pp. C748-C759 ◽  
Author(s):  
Takahiro Shimizu ◽  
Takahiro Iehara ◽  
Kaori Sato ◽  
Takuto Fujii ◽  
Hideki Sakai ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Reversal Potential ◽  
Bathing Solution ◽  
Osmotic Swelling ◽  
Cl Channel ◽  
Whole Cell Patch Clamp ◽  
Current Voltage ◽  
Intracellular Ca ◽  
Current Voltage Relationship ◽  
Voltage Relationship

TMEM16 (transmembrane protein 16) proteins, which possess eight putative transmembrane domains with intracellular NH2- and COOH-terminal tails, are thought to comprise a Cl− channel family. The function of TMEM16F, a member of the TMEM16 family, has been greatly controversial. In the present study, we performed whole cell patch-clamp recordings to investigate the function of human TMEM16F. In TMEM16F-transfected HEK293T cells but not TMEM16K- and mock-transfected cells, activation of membrane currents with strong outward rectification was found to be induced by application of a Ca2+ ionophore, ionomycin, or by an increase in the intracellular free Ca2+ concentration. The free Ca2+ concentration for half-maximal activation of TMEM16F currents was 9.6 μM, which is distinctly higher than that for TMEM16A/B currents. The outwardly rectifying current-voltage relationship for TMEM16F currents was not changed by an increase in the intracellular Ca2+ level, in contrast to TMEM16A/B currents. The Ca2+-activated TMEM16F currents were anion selective, because replacing Cl− with aspartate− in the bathing solution without changing cation concentrations caused a positive shift of the reversal potential. The anion selectivity sequence of the TMEM16F channel was I− > Br− > Cl− > F− > aspartate−. Niflumic acid, a Ca2+-activated Cl− channel blocker, inhibited the TMEM16F-dependent Cl− currents. Neither overexpression nor knockdown of TMEM16F affected volume-sensitive outwardly rectifying Cl− channel (VSOR) currents activated by osmotic swelling or apoptotic stimulation. These results demonstrate that human TMEM16F is an essential component of a Ca2+-activated Cl− channel with a Ca2+ sensitivity that is distinct from that of TMEM16A/B and that it is not related to VSOR activity.

scholarly journals Voltage-dependent block of cardiac inward-rectifying potassium current by monovalent cations.

1989 ◽  
Vol 94 (2) ◽  
pp. 349-361 ◽  
Author(s):  
R D Harvey ◽  
R E Ten Eick
Keyword(s):  
Ventricular Myocytes ◽  
Negative Slope ◽  
Voltage Sensitivity ◽  
Dependent Manner ◽  
Inward Current ◽  
Current Voltage ◽  
Steady State Current ◽  
Voltage Dependent ◽  
Current Block ◽  
K Current

The inward-rectifying K+ current (IK1) in cat ventricular myocytes, like inward-rectifying K+ currents in many other preparations, exhibited a negative slope conductance region at hyperpolarized membrane potentials that was time-dependent. This was evident as an inactivation of inward current elicited by hyperpolarizing voltage-clamp pulses resulting in a negative slope region of the steady-state current-voltage relationship at potentials negative to -140 mV. Removing extracellular Na+ prevented the development of the negative slope in this voltage region, suggesting that Na+ can block IK1 channels in a time- and voltage-dependent manner. The time and voltage dependence of Cs+-induced block of IK1 was also examined. Cs+ blocked inward current in a manner similar to that of Na+, but the former was much more potent. The fraction of current blocked by Cs+ in the presence of Na+ was reduced in a time- and voltage-dependent manner, which suggested that these blocking ions compete for a common or at least similar site of action. In the absence of Na+, inactivation of IK1 could also be induced by both Cs+ and Li+. However, Li+ was less potent than Na+ in this respect. Calculation of the voltage sensitivity of current block by each of these ions suggests that the mechanism of block by each is similar.

Glutamatergic neuromuscular transmission in the heart of the isopod crustacean Ligia exotica.

1998 ◽  
Vol 201 (20) ◽  
pp. 2833-2842 ◽  
Author(s):  
A Sakurai ◽  
A Mori ◽  
H Yamagishi
Keyword(s):  
Cardiac Muscle ◽  
Neuromuscular Transmission ◽  
Reversal Potential ◽  
Induced Response ◽  
Cardiac Ganglion ◽  
Axon Terminals ◽  
Current Voltage ◽  
Specific Antagonist ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Neuromuscular transmission between the cardiac ganglion (CG) and the myocardium was examined in the adult heart of the isopod crustacean Ligia exotica. Intracellular injection of neurobiotin into the CG neurones revealed that all six CG neurones send their axons onto the cardiac muscle, where they form axon terminals bearing varicosities. All the CG neurones and their processes exhibited glutamate-like immunoreactivity. The cardiac muscle showed depolarizing membrane potential responses to glutamate applied focally to sites close to axon terminals bearing varicosities. Both the glutamate-induced response and the excitatory junctional potential (EJP) showed desensitization in response to the repeated application of glutamate. Under voltage-clamp conditions, the cardiac muscle produced inward current responses to focally applied glutamate. The reversal potential for the glutamate-induced current estimated from extrapolation of the linear current/voltage relationship was similar to that of the excitatory junctional current evoked by ganglionic nerve stimulation. Both the glutamate-induced response and the EJP were blocked by a glutamate-specific antagonist, Joro spider toxin. These results led us to conclude that the CG neurones of Ligia exotica are glutamatergic motoneurones.

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.

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