Relative contributions of passive equilibrium and active transport to the distribution of chloride in mammalian cortical neurons

1988 ◽  
Vol 60 (1) ◽  
pp. 105-124 ◽  
Author(s):  
S. M. Thompson ◽  
R. A. Deisz ◽  
D. A. Prince
Keyword(s):  
Time Constant ◽  
Cortical Neurons ◽  
Time Course ◽  
Chloride Concentration ◽  
Reversal Potential ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Gamma Aminobutyric Acid ◽  
The Mean ◽  
Mean Time

1. Active and passive factors affecting the chloride gradient of cortical neurons were assessed using intracellular recordings from neurons in slices of cingulate cortex maintained in vitro. The chloride equilibrium potential (ECl-) was estimated indirectly from the reversal potentials of responses to perisomatic gamma-aminobutyric acid (GABA) application and the Cl(-)-dependent inhibitory postsynaptic potential (IPSP). Under control conditions the mean resting potential (Vm; -69.7 mV) was not significantly different than the mean IPSP reversal potential (EIPSP; -70.1 mV). 2. Increasing the external potassium concentration ([K+]o) from 1 to 10 mM shifted the mean EIPSP from -80.4 to -61.8 mV. The mean EIPSP was approximately equal to the mean Vm at all [K+]oS. The conditions of Donnan equilibrium are not met in [K+]o less than 10 mM. 3. Polarization of Vm up to 20 mV away from EIPSP for 4 min with maintained current injection had no significant effect on EIPSP. 4. The GABA reversal potential was maintained 37-52 mV less negative than Vm after equilibration in saline in which the external chloride concentration had been reduced from 133 to 5 mM by substitution with isethionate. Vm and input resistance were not significantly different from control values in cells recorded under these conditions. 5. We conclude that Cl- is not passively distributed in cortical neurons, perhaps due to a low resting Cl- permeability. 6. Impalement with electrodes containing 2 M KCl resulted in a rapid 10 mV depolarizing shift in EIPSP that then remained relatively constant. Intracellular iontophoresis of Cl- resulted in a further depolarizing shift of EIPSP of 5-10 mV that returned to control in less than 1 min. The time course of recovery of IPSP amplitude could be fit with a single exponential having a mean time constant of 6.9 +/- 1.5 s and was independent of the amount of Cl- injected or stimulation frequency. 7. Reductions in temperature from 37 to 32 degrees C significantly increased the mean time constant of IPSP recovery from Cl- injection to 11.1 +/- 3.3 s, corresponding to Q10 = 2.6.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Shift of Intracellular Chloride Concentration in Ganglion and Amacrine Cells of Developing Mouse Retina

2006 ◽  
Vol 95 (4) ◽  
pp. 2404-2416 ◽  
Author(s):  
Ling-Li Zhang ◽  
Hemal R. Pathak ◽  
Douglas A. Coulter ◽  
Michael A. Freed ◽  
Noga Vardi
Keyword(s):  
Gaba Receptors ◽  
Chloride Concentration ◽  
Reversal Potential ◽  
Amacrine Cells ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Mouse Retina ◽  
Intracellular Chloride ◽  
Excitatory Action ◽  
Intracellular Chloride Concentration

GABA and glycine provide excitatory action during early development: they depolarize neurons and increase intracellular calcium concentration. As neurons mature, GABA and glycine become inhibitory. This switch from excitation to inhibition is thought to result from a shift of intracellular chloride concentration ([Cl−]i) from high to low, but in retina, measurements of [Cl−]i or chloride equilibrium potential ( ECl) during development have not been made. Using the developing mouse retina, we systematically measured [Cl−]i in parallel with GABA's actions on calcium and chloride. In ganglion and amacrine cells, fura-2 imaging showed that before postnatal day (P) 6, exogenous GABA, acting via ionotropic GABA receptors, evoked calcium rise, which persisted in HCO3−- free buffer but was blocked with 0 extracellular calcium. After P6, GABA switched to inhibiting spontaneous calcium transients. Concomitant with this switch we observed the following: 6-methoxy- N-ethylquinolinium iodide (MEQ) chloride imaging showed that GABA caused an efflux of chloride before P6 and an influx afterward; gramicidin-perforated-patch recordings showed that the reversal potential for GABA decreased from −45 mV, near threshold for voltage-activated calcium channel, to −60 mV, near resting potential; MEQ imaging showed that [Cl−]i shifted steeply around P6 from 29 to 14 mM, corresponding to a decline of ECl from −39 to −58 mV. We also show that GABAergic amacrine cells became stratified by P4, potentially allowing GABA's excitatory action to shape circuit connectivity. Our results support the hypothesis that a shift from high [Cl−]i to low causes GABA to switch from excitatory to inhibitory.

Characterization of spontaneous and evoked inhibitory postsynaptic potentials in rat supraoptic neurosecretory neurons in vitro

1986 ◽  
Vol 56 (6) ◽  
pp. 1703-1717 ◽  
Author(s):  
J. C. Randle ◽  
C. W. Bourque ◽  
L. P. Renaud
Keyword(s):  
Membrane Potential ◽  
Time Constant ◽  
Reversal Potential ◽  
Chloride Ions ◽  
Membrane Potentials ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials ◽  
Neurosecretory Neurons ◽  
The Mean ◽  
Mean Time

Intracellular recordings from 52 supraoptic nucleus neurosecretory neurons in perfused explants of rat hypothalamus revealed abundant spontaneous inhibitory postsynaptic potentials (sIPSPs) and a compound evoked inhibitory postsynaptic potential (eIPSP) following electrical stimulation in the diagonal band of Broca (DBB). These IPSPs were characterized in terms of the magnitude and ionic specificity of the underlying current and in terms of the transmitter responsible for their activation. sIPSPs rose rapidly to peak within 3-5 ms and decayed exponentially with a mean time constant of 20.2 +/- 1.9 ms (mean +/- SE), a value 1.6-fold greater than the mean cell time constant of 13.8 +/- 1.0 ms. The eIPSPs rose rapidly to peak within 3-10 ms and decayed exponentially over 60-100 ms with a mean time constant of 37.0 +/- 2.8 ms, which is 2.6-fold greater than the mean cell time constant. These features imply a brief persistence of the conductance underlying the IPSPs. In recordings with KAcetate-filled micropipettes, sIPSPs were hyperpolarizing at membrane potentials in the range of -50 to -70 mV and reversed polarity when the membrane was hyperpolarized beyond -80 mV. The mean reversal potential (EsIPSP) was -72.4 +/- 1.1 mV. eIPSPs were hyperpolarizing at resting membrane potential and could be reversed by membrane hyperpolarization beyond a mean reversal potential (EIPSP) of -67.4 +/- 1.4 mV. In recordings with KCl-filled micropipettes, sIPSPs were depolarizing at all membrane potentials more negative than -50 mV. Under these conditions, EsIPSP was estimated at -44 mV. sIPSPs were absent when chloride ions were removed from the perfusion medium. eIPSPs were depolarizing at all membrane potentials and often evoked action potentials; mean EeIPSP was 43.2 mV. Reversal potentials of spontaneous and evoked IPSPs were similar. At a given membrane potential, sIPSP amplitudes varied widely between 1 and 20 mV. The conductance increase underlying individual sIPSPs was estimated to vary between 0.17 and 3.0 nS (avg 0.6 nS) against a mean resting input conductance of 3.78 +/- 0.41 nS. Estimates of the conductance underlying eIPSPs varied widely between cells, from 0.8 to 22.0 nS (mean 72 nS). Accordingly, the ratio of evoked to spontaneous IPSP conductance varied from 1.6 to 43.7 (mean 13.1). The reversal potential of evoked IPSPs shifted with the extracellular concentration of Cl- ions ([Cl-]0) with a mean slope of 41 mV/log [Cl-]0.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacology of a Slowly Inactivating Outward Current in Hippocampal CA3 Pyramidal Neurons

2006 ◽  
Vol 96 (3) ◽  
pp. 1116-1123 ◽  
Author(s):  
Riccardo Bianchi ◽  
Shih-Chieh Chuang ◽  
Robert K. S. Wong
Keyword(s):  
Time Course ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Outward Current ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Transient Outward Current ◽  
Activation Threshold

The pharmacology of a slowly inactivating outward current was examined using whole cell patch-clamp recordings in CA3 pyramidal cells of guinea pig hippocampal slices. The current had a low activation threshold (about −60 mV) and inactivated slowly (time constant of 3.4 ± 0.5 s at −50 mV) and completely at membrane voltages depolarized to −50 mV. The slowly inactivating outward current was mainly mediated by K+ with a reversal potential close to the equilibrium potential for K+. The slowly inactivating outward current had distinct pharmacological properties: its time course was not affected by extracellular Cs+ (1 mM) or 4-AP (1–5 mM)—broad spectrum inhibitors of K+ currents and of inactivating K+ currents, respectively. The presence of extracellular Mn2+ (0.5–1 mM), which suppresses several Ca2+-dependent K+ currents, also did not affect the slowly inactivating outward current. The current was partially suppressed by TEA (50 mM) and was blocked by intracellular Cs+ (134 mM). In addition, intracellular QX-314 (5 mM), a local anesthetic derivative, inhibited this current. The slowly inactivating outward current with its low activation threshold should be operational at the resting potential. Our results suggest that the transient outward current activated at subthreshold membrane potentials in hippocampal pyramidal cells consists of at least three components. In addition to the well-described A- and D-currents, the slowest decaying component reflects the time course of a distinct current, suppressible by QX-314.

Neuromuscular Transmission in the Longitudinal Layer of Somatic Muscle in the Earthworm

1969 ◽  
Vol 50 (2) ◽  
pp. 417-430
Author(s):  
T. HIDAKA ◽  
Y. ITO ◽  
H. KURIYAMA ◽  
N. TASHIRO
Keyword(s):  
Time Course ◽  
Longitudinal Muscle ◽  
Chloride Concentration ◽  
Reversal Potential ◽  
Membrane Conductance ◽  
Equilibrium Potential ◽  
Muscle Fibres ◽  
Free Solution ◽  
Excitatory Junction Potentials ◽  
Potential Level

1. The properties of the miniature inhibitory junction potentials (M.I.J.P.) and the inhibitory junction potentials (I.J.P.) elicited by nerve stimulation were investigated in longitudinal muscle fibres of the earthworm. 2. Histograms of the amplitudes(mean,0.71mV.) and the intervals (mean, 101 msec.) of the M.I.J.P. showed skew curves. 3. The polarity of the M.I.J.P. was reversed at about -60 mV. When the external chloride was substituted by glutamate the M.I.J.P. disappeared as an external chloride concentration of 15-20 mM, and further reduction reversed their polarity. 4. Picrotoxin blocked generation of the M.I.J.P. and the I.J.P. 5. The cross-over point of the current-voltage relation curves, with and without presence of GABA, occurred at a membrane potential of -54 mV. in potassium-free solution, and at -56 mV. in potassium-excess solution. 6. Iontophoretic application of GABA produced slow hyperpolarization. The equilibrium potential of the GABA-potential was about -60 mV. During the time course of the GABA-potentials an increase in the membrane conductance was observed. 7. Miniature excitatory junction potentials (M.E.J.P.) and excitatory junction potentials (E.J.P.) could be recorded from the longitudinal muscle, but the M.E.J.P. were rare. 8. D-tubocurarine, but not atropine, completely blocked the M.E.J.P. and E.J.P. Prostigmine enhanced their amplitude and duration. 9. The reversal potential level for the E.J.P. was about 0 mV. Sodium-free solution lowered the reversal potential level for the M.E.J.P. to -20 mV.

Metabolic control of Argyropelecus hemigymnus photophores: effects of glucose and pyruvate

1991 ◽  
Vol 69 (9) ◽  
pp. 2410-2413 ◽  
Author(s):  
J. Mallefet ◽  
F. Baguet
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Uptake ◽  
Metabolic Control ◽  
Time Course ◽  
Light Emission ◽  
Mesopelagic Fish ◽  
Fresh Weight ◽  
Hypometabolic State ◽  
The Mean ◽  
Mean Time

Modifications in oxygen consumption and luminescence of isolated luminescent organs of the mesopelagic fish Argyropelecus hemigymnus following glucose and pyruvate administration were studied before and during light emission triggered by adrenaline. Isolated photophores (mean fresh weight 13.5 ± 0.9 mg) at rest, i.e., in the absence of light emission, in saline (20 °C) exhibit a respiration rate of 1.045 ± 0.082 (SE) nmol O2/min (n = 35). A significant decrease (p = 0.05) in oxygen consumption was observed after the addition of 5.5 mM glucose. Instead of the oxygen decrease usually observed as a result of control stimulations using adrenaline, photophores pretreated with glucose increased their oxygen uptake in response to adrenaline, and maximal light emission was reduced by 85% (p = 0.01). The addition of 5.5 mM pyruvate induced a significant transient increase (p = 0.05) in oxygen uptake of isolated photophores, though this treatment did not statistically modify the mean time course of oxygen consumption and light emission in response to adrenaline. The hypothesis of a hypometabolic state of the isolated photophores of A. hemigymnus during light emission is discussed.

Possible Effects of Depolarizing GABAA Conductance on the Neuronal Input–Output Relationship: A Modeling Study

2005 ◽  
Vol 93 (6) ◽  
pp. 3504-3523 ◽  
Author(s):  
Kenji Morita ◽  
Kunichika Tsumoto ◽  
Kazuyuki Aihara
Keyword(s):  
Firing Rate ◽  
Cortical Neurons ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Input Output ◽  
Wide Range ◽  
The Relationship

Recent in vitro experiments revealed that the GABAA reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input–output relationship in a simple conductance-based model of cortical neurons with the depolarized GABAA reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo–like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input–output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABAA reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation.

Synchronization properties of spindle oscillations in a thalamic reticular nucleus model

1994 ◽  
Vol 72 (3) ◽  
pp. 1109-1126 ◽  
Author(s):  
D. Golomb ◽  
X. J. Wang ◽  
J. Rinzel
Keyword(s):  
Time Course ◽  
Cluster State ◽  
Large Population ◽  
Reversal Potential ◽  
Ionic Currents ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Quiescent State ◽  
Gamma Aminobutyric Acid ◽  
Cluster States

1. We address the hypothesis of Steriade and colleagues that the thalamic reticular nucleus (RE) is a pacemaker for thalamocortical spindle oscillations by developing and analyzing a model of a large population of all-to-all coupled inhibitory RE neurons. 2. Each RE neuron has three ionic currents: a low-threshold T-type Ca2+ current (ICa-T), a calcium-activated potassium current (IAHP) and a leakage current (IL). ICa-T underlies a cell's postinhibitory rebound properties, whereas IAHP hyperpolarizes the neuron after a burst. Each neuron, which is a conditional oscillator, is coupled to all other RE neurons via fast gamma-aminobutyric acid-A (GABAA) and slow GABAB synapses. 3. For generating network oscillations IAHP may not be necessary. Synaptic inhibition can provide the hyperpolarization for deinactivating ICa-T that causes bursting if the reversal potentials for GABAA and GABAB synapses are sufficiently negative. 4. If model neurons display sufficiently powerful rebound excitability, an isolated RE network of such neurons oscillates with partial but typically not full synchrony. The neurons spontaneously segregate themselves into several macroscopic clusters. The neurons within a cluster follow the same time course, but the clusters oscillate differently from one another. In addition to activity patterns in which clusters burst sequentially (e.g., 2 or 3 clusters bursting alternately), a two-cluster state may occur with one cluster active and one quiescent. Because the neurons are all-to-all coupled, the cluster states do not have any spatial structure. 5. We have explored the sensitivity of such partially synchronized patterns to heterogeneity in cells' intrinsic properties and to simulated neuroelectric noise. Although either precludes precise clustering, modest levels of heterogeneity or noise lead to approximate clustering of active cells. The population-averaged voltage may oscillate almost regularly but individual cells burst at nearly every second cycle or less frequently. The active-quiescent state is not robust at all to heterogeneity or noise. Total asynchrony is observed when heterogeneity or noise is too large, e.g., even at 25% heterogeneity for our reference set of parameter values. 6. The fast GABAA inhibition (with a reversal potential more negative than, say, -65 mV) favors the cluster states and prevents full synchrony. Our simulation results suggest two mechanisms that can fully synchronize the isolated RE network model. With GABAA removed or almost totally blocked, GABAB inhibition (because it is slow) can lead to full synchrony, which is partially robust to heterogeneity and noise.(ABSTRACT TRUNCATED AT 400 WORDS)

Control of intracellular calcium by membrane potential in human melanoma cells

1993 ◽  
Vol 265 (6) ◽  
pp. C1501-C1510 ◽  
Author(s):  
B. Nilius ◽  
G. Schwarz ◽  
G. Droogmans
Keyword(s):  
Cell Proliferation ◽  
Membrane Potential ◽  
Intracellular Calcium ◽  
Reversal Potential ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Patch Clamp Technique ◽  
Human Melanoma Cells

The modulation of intracellular calcium ([Ca2+]i) by the membrane potential was investigated in human melanoma cells by combining the nystatin-perforated patch-clamp technique with Ca2+ measurements. Voltage steps to -100 mV induced a rise in [Ca2+]i and a creeping inward current. These effects were absent in Ca(2+)-free solution and could be blocked by Ni2+ or La3+. Voltage ramps revealed a close correlation between [Ca2+]i and voltage, with the strongest voltage dependence around the resting potential. Long-lasting tail currents, closely correlated with the rise in [Ca2+]i and a reversal potential close to the K+ equilibrium potential, occurred if the membrane potential was clamped back to 0 mV. They were absent if intracellular K+ was replaced by Cs+ and blocked by extracellular tetraethylammonium (5 mM), Ba2+ (1 mM), or a membrane-permeable adenosine 3',5'-cyclic monophosphate analogue. These observations are discussed in relation to cell proliferation. The enhanced expression of K+ channels during cell proliferation provides a positive-feedback mechanism resulting in long-term changes in [Ca2+]i required for the G1-S transition in the cell cycle.

scholarly journals Outward current in single smooth muscle cells of the guinea pig taenia coli.

1989 ◽  
Vol 93 (3) ◽  
pp. 551-564 ◽  
Author(s):  
Y Yamamoto ◽  
S L Hu ◽  
C Y Kao
Keyword(s):  
Guinea Pig ◽  
Time Constant ◽  
Time Course ◽  
Reversal Potential ◽  
Outward Current ◽  
Enzymatic Digestion ◽  
Taenia Coli ◽  
Physiological Conditions ◽  
Dependent Component ◽  
Voltage Dependent

In single myocytes of the guinea pig taenia coli, dispersed by enzymatic digestion, the late outward current is carried by K+. It has both a Ca2+-activated component and a voltage-dependent component which is resistant to external Co2+. The reversal potential is -84 mV, and the channel(s) for it are highly selective to K+. At 33 degrees C, the activation follows n2 kinetics, with a voltage-dependent time constant of 10.6 ms at 0 mV, which shortens to 1.7 ms at +70 mV. Deactivation follows a single-exponential time course, with a voltage-dependent time constant of 11 ms at -50 mV, which lengthens to 33 ms at -20 mV. During a 4.5-s maintained depolarization, IK inactivates, most of it into two exponential components, but there is a small noninactivating residue. It is surmised that during an action potential under physiological conditions, there is sufficient IK to cause repolarization.

Contribution of changes in the chloride driving force to the fading of I GABA in frog melanotrophs

2000 ◽  
Vol 278 (3) ◽  
pp. E430-E443 ◽  
Author(s):  
Frank le Foll ◽  
Olivier Soriani ◽  
Hubert Vaudry ◽  
Lionel Cazin
Keyword(s):  
Driving Force ◽  
Chloride Concentration ◽  
Reversal Potential ◽  
Resting Potential ◽  
Perforated Patch ◽  
Induced Currents ◽  
Patch Configuration ◽  
Intracellular Chloride Concentration ◽  
Current Reversal

Chloride redistribution during type A γ-aminobutyric acid (GABAA) currents ( I GABA) has been investigated in cultured frog pituitary melanotrophs with imposed intracellular chloride concentration ([Cl−]i) in the whole cell configuration or with unaltered [Cl−]i using the gramicidin-perforated patch approach. Prolonged GABA exposures elicited reproducible decaying currents. The decay of I GABAwas associated with both a transient fall of conductance ( g GABA) and shift of current reversal potential ( E GABA). The shift of E GABAappeared to be time and driving force dependent. In the gramicidin-perforated patch configuration, repeated GABA exposures induced currents that gradually vanished. The fading of I GABA was due to persistent shifts of E GABA as a result of g GABArecovering from one GABA application to another. In cells alternatively clamped at potentials closely flanking resting potential and submitted to a train of brief GABA pulses, a reversal of I GABA was observed after 150 s recording. It is demonstrated that, in intact frog melanotrophs, shifts of E GABA combine with genuine receptor desensitization to depress I GABA. These findings strongly suggest that shifts of E GABA may act as a negative feedback, reducing the bioelectrical and secretory responses induced by an intense release of GABA in vivo.

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