Membrane potential and ion concentration stability conditions for a cell with a restricted extracellular space

1979 ◽  
Vol 206 (1163) ◽  
pp. 145-161 ◽  

For an isolated membrane, the resting (zero current) potential is stable if the slope conductance is positive, and is unstable if the slope conductance is negative. Recent work suggests that the properties of many preparations are influenced by the presence of an extracellular space that is not in good diffusive contact with the bulk extracellular fluid. Ionic current flow across the membrane changes the ion concentrations in this space. These concen­tration changes affect the stability of the membrane potential. Even if the slope conductance is negative, the presence of the extracellular space can confer stability on the resting potential. Conversely, even if the slope conductance is positive, the extracellular space can produce instability of the resting potential. Evaluation of the relevant parameters for cardiac Purkinje fibres, from published experimental data, suggests that concen­tration changes in the extracellular space may play a significant role in determining when an action potential is initiated.

1977 ◽  
Vol 55 (3) ◽  
pp. 709-723 ◽  
Author(s):  
J. G. Foulks ◽  
Florence A. Perry

The electrical and mechanical behaviour of frog twitch muscle in response to changes in membrane potential has been examined over a wide range of hydrogen ion concentration (pH 3.0–11.0). The changes in resting and action potentials, twitches, and maximum potassium-induced contractures (K contractures) were remarkably small when the pH was varied between 5.0 and 10.0. The time course of action potentials generally displayed small graded changes with variation in pH, possibly as the result of changes in surface potential.The amplitude of twitches and maximum K contractures was substantially decreased when pH was reduced to 4.0 or raised to 11.0 without significant alteration in membrane resting potential or consistent suppression of excitation, but maximum caffeine-induced contractures were unchanged. Replacement of chloride with perchlorate promptly antagonized the depressant effects of pH extremes (4.0, 11.0) on both twitch amplitude and maximum K-contracture tension. Acid-induced reductions in maximum K-contracture tension also were partially antagonized by increased calcium concentration. The onset and recovery from the contraction-depressant effects of pH extremes were too slow to be explained by the titration of groups immediately accessible at the membrane surface but too rapid to be accounted for by changes in intracellular pH. Thus, excitation and contraction apparently were uncoupled by sufficient alteration in extracellular pH. Changes in external pH had little effect on the impairment of maximum K contractures by media lacking divalent cations, or on the restoration of such responses by perchlorate except at very alkaline pH (10.0–11.0).The threshold for K contractures was reduced at pH 11.0, but otherwise was little affected by variation in pH at normal concentrations of divalent cations. Altered pH did not modify the usual effects of increased calcium concentration on the relation between potassium concentration and K-contracture tension. When K contractures were maintained by perchlorate in the absence of divalent cations, hydrogen ions displayed calcium-like actions on the relation between external K concentration ([K]0) and K-contracture tension, and also on the time course of submaximum K contractures. These observations are compatible with similar effects of hydrogen and calcium ions on surface potential.The problem of identifying putative charged groups which might influence the linkage between contractile responses and changes in membrane potential is discussed.


1990 ◽  
Vol 259 (3) ◽  
pp. C402-C408 ◽  
Author(s):  
E. P. Burke ◽  
K. M. Sanders

Previous studies have suggested that the membrane potential gradient across the circular muscle layer of the canine proximal colon is due to a gradient in the contribution of the Na(+)-K(+)-ATPase. Cells at the submucosal border generate approximately 35 mV of pump potential, whereas at the myenteric border the pump contributes very little to resting potential. Results from experiments in intact muscles in which the pump is blocked are somewhat difficult to interpret because of possible effects of pump inhibitors on membrane conductances. Therefore, we studied isolated colonic myocytes to test the effects of ouabain on passive membrane properties and voltage-dependent currents. Ouabain (10(-5) M) depolarized cells and decreased input resistance from 0.487 +/- 0.060 to 0.292 +/- 0.040 G omega. The decrease in resistance was attributed to an increase in K+ conductance. Studies were also performed to measure the ouabain-dependent current. At 37 degrees C, in cells dialyzed with 19 mM intracellular Na+ concentration [( Na+]i), ouabain caused an inward current averaging 71.06 +/- 7.49 pA, which was attributed to blockade of pump current. At 24 degrees C or in cells dialyzed with low [Na+]i (11 mM), ouabain caused little change in holding current. With the input resistance of colonic cells, pump current appears capable of generating at least 35 mV. Thus an electrogenic Na+ pump could contribute significantly to membrane potential.


2000 ◽  
Vol 78 (5) ◽  
pp. 378-391 ◽  
Author(s):  
G V Obrocea ◽  
M E Morris

Ion-selective microelectrode recordings were made to assess a possible contribution of extracellular γ-aminobutyric acid (GABA) accumulation to early responses evoked in the brain by anoxia and ischemia. Changes evoked by GABA or N2 in [K+]o, [Cl-]o, [Na+]o, and [TMA+]o were recorded in the cell body and dendritic regions of the stratum pyramidale (SP) and stratum radiatum (SR), respectively, of pyramidal neurons in CA1 of guinea pig hippocampal slices. Bath application of GABA (1-10 mM) for approximately 5 min evoked changes in [K+]o and [Cl-]o with respective EC50 levels of 3.8 and 4.1 mM in SP, and 4.7 and 5.6 mM in SR. In SP 5 mM GABA reversibly increased [K+]o and [Cl-]o and decreased [Na+]o; replacement of 95% O2 -5% CO2 by 95% N2 -5% CO2 for a similar period of time evoked changes which were for each ion in the same direction as those with GABA. In SR both GABA and N2 caused increases in [K+]o and decreases in [Cl-]o and [Na+]o. The reduction of extracellular space, estimated from levels of [TMA+]o during exposures to GABA and N2, was 5-6% and insufficient to cause the observed changes in ion concentration. Ion changes induced by GABA and N2 were reversibly attenuated by the GABAA receptor antagonist bicuculline methiodide (BMI, 100 µM). GABA-evoked changes in [K+]o in SP and SR and [Cl-]o in SP were depressed by >=90%, and of [Cl-]o in SR by 50%; N2-evoked changes in [K+]o in SP and SR were decreased by 70% and those of [Cl-]o by 50%. BMI blocked Δ [Na+]o with both GABA and N2 by 20-30%. It is concluded that during early anoxia: (i) accumulation of GABA and activation of GABAA receptors may contribute to the ion changes and play a significant role, and (ii) responses in the dendritic (SR) regions are greater than and (or) differ from those in the somal (SP) layers. A large component of the [K+]o increase may involve a GABA-evoked Ca2+-activated gk, secondary to [Ca2+]i increase. A major part of [Cl-]o changes may arise from GABA-induced gCl and glial efflux, with strong stimulation of active outward transport and anion exchange at SP, and inward Na+/K+/2Cl- co-transport at SR. Na+ influx is attributable mainly to Na+-dependent transmitter uptake, with only a small amount related to GABAA receptor activation. Although the release and (or) accumulation of GABA during anoxia might be viewed as potentially protectant, the ultimate role may more likely be an important contribution to toxicity and delayed neuronal death. Key words: brain slices, ion-selective microelectrodes, stratum pyramidale, stratum radiatum, bicuculline methiodide, extracellular space shrinkage.


2017 ◽  
Vol 24 (07) ◽  
pp. 1850019
Author(s):  
DING WU-QUAN ◽  
HE JIA-HONG ◽  
WANG LEI ◽  
LIU XIN-MIN ◽  
LI HANG

The study of soil colloids is essential because the stability of soil colloidal particles are important processes of interest to researchers in environmental fields. The strong nonclassical polarization of the adsorbed cations (Na[Formula: see text] and K[Formula: see text] decreased the electric field and the electrostatic repulsion between adjacent colloidal particles. The decrease of the absolute values of surface potential was greater for K[Formula: see text] than for Na[Formula: see text]. The lower the concentration of Na[Formula: see text] and K[Formula: see text] in soil colloids, the greater the electrostatic repulsion between adjacent colloidal particles. The net pressure and the electrostatic repulsion was greater for Na[Formula: see text] than for K[Formula: see text] at the same ion concentration. For K[Formula: see text] and Na[Formula: see text] concentrations higher than 50[Formula: see text]mmol L[Formula: see text] or 100 mmol L[Formula: see text], there was a net negative (or attractive) pressure between two adjacent soil particles. The increasing total average aggregation (TAA) rate of soil colloids with increasing Na[Formula: see text] and K[Formula: see text] concentrations exhibited two stages: the growth rates of TAA increased rapidly at first and then increased slowly and eventually almost negligibly. The critical coagulation concentrations of soil colloids in Na[Formula: see text] and K[Formula: see text] were 91.6[Formula: see text]mmol L[Formula: see text] and 47.8[Formula: see text]mmol L[Formula: see text], respectively, and these were similar to the concentrations at the net negative pressure.


1991 ◽  
Vol 97 (6) ◽  
pp. 1165-1186 ◽  
Author(s):  
R Payne ◽  
B V Potter

Limulus ventral photoreceptors contain calcium stores sensitive to release by D-myo-inositol 1,4,5 trisphosphate (InsP3) and a calcium-activated conductance that depolarizes the cell. Mechanisms that terminate the response to InsP3 were investigated using nonmetabolizable DL-myo-inositol 1,4,5 trisphosphorothioate (InsPS3). An injection of 1 mM InsPS3 into a photoreceptor's light-sensitive lobe caused an initial elevation of cytosolic free calcium ion concentration (Cai) and a depolarization lasting only 1-2 s. A period of densensitization followed, during which injections of InsPS3 were ineffective. As sensitivity recovered, oscillations of membrane potential began, continuing for many minutes with a frequency of 0.07-0.3 Hz. The activity of InsPS3 probably results from the D-stereoisomer, since L-InsP3 was much less effective than InsP3. Injections of 1 mM InsP3 caused an initial depolarization and a period of densensitization similar to that caused by 1 mM InsPS3, but no sustained oscillations of membrane potential. The initial response to InsPS3 or InsP3 may therefore be terminated by densensitization, rather than by metabolism. Metabolism of InsP3 may prevent oscillations of membrane potential after sensitivity has recovered. The InsPS3-induced oscillations of membrane potential accompanied oscillations of Cai and were abolished by injection of ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid. Removal of extracellular calcium reduced the frequency of oscillation but not its amplitude. Under voltage clamp, oscillations of inward current were observed. These results indicate that periodic bursts of calcium release underly the oscillations of membrane potential. After each burst, the sensitivity of the cell to injected InsP3 was greatly reduced, recovering during the interburst interval. The oscillations may, therefore, result in part from a periodic variation in sensitivity to a constant concentration of InsPS3. Prior injection of calcium inhibited depolarization by InsPS3, suggesting that feedback inhibition of InsPS3-induced calcium release by elevated Cai may mediate desensitization between bursts and after injections of InsPS3.


1988 ◽  
Vol 254 (3) ◽  
pp. C423-C431 ◽  
Author(s):  
H. Yamaguchi ◽  
T. W. Honeyman ◽  
F. S. Fay

Studies were carried out to determine the effects of the beta-adrenergic agent, isoproterenol (ISO), on membrane electrical properties in single smooth muscle cells enzymatically dispersed from toad stomach. In cells bathed in buffer of physiological composition, the average resting potential was -56.4 +/- 1.4 mV (mean +/- SE, n = 35). The dominant effect of exposure to ISO was hyperpolarization. The hyperpolarization was apparent in all cells studied and averaged 11.6 +/- 1.2 mV (n = 27). In the majority of the cells, hyperpolarization was accompanied by a decreased input resistance (Rin). Often the change in resistance appeared to lag behind the change in membrane potential. The lack of coincident changes in membrane potential and resistance may reflect a superposition of the outward rectification properties of the membrane on beta-adrenergic-induced increases in ionic conductance. In about half of the cells, an initial small depolarization (3.1 +/- 0.3 mV, n = 14) was accompanied by a small but distinct increase in Rin (12 +/- 2.5%). When membrane potential was made more negative than the estimated equilibrium potential for K+ (EK) by injection of current, ISO also produced biphasic effects, an initial hyperpolarization which reversed to a sustained depolarization to a value (-90 mV) near the estimated EK. The hyperpolarization by ISO could be diminished in a time-dependent manner by previous exposure to ouabain. The inhibition by ouabain, however, appeared to be a fortuitous result of glycoside-induced positive shifts in EK. These observations indicate that the dominant electrophysiological effect of beta-adrenergic stimuli is to hyperpolarize the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)


1997 ◽  
Vol 78 (5) ◽  
pp. 2235-2245 ◽  
Author(s):  
Xiao Wen Fu ◽  
Borys L. Brezden ◽  
Shu Hui Wu

Fu, Xiao Wen, Borys L. Brezden, and Shu Hui Wu. Hyperpolarization-activated inward current in neurons of the rat's dorsal nucleus of the lateral lemniscus in vitro. J. Neurophysiol. 78: 2235–2245, 1997. The hyperpolarization-activated current ( I h) underlying inward rectification in neurons of the rat's dorsal nucleus of the lateral lemniscus (DNLL) was investigated using whole cell patch-clamp techniques. Patch recordings were made from DNLL neurons of young rats (21–30 days old) in 400 μm tissue slices. Under current clamp, injection of negative current produced a graded hyperpolarization of the cell membrane, often with a gradual sag in the membrane potential toward the resting value. The rate and magnitude of the sag depended on the amount of hyperpolarizing current. Larger current resulted in a larger and faster decay of the voltage. Under voltage clamp, hyperpolarizing voltage steps elicited a slowly activating inward current that was presumably responsible for the sag observed in the voltage response to a steady hyperpolarizing current recorded under current clamp. Activation of the inward current ( I h) was voltage and time dependent. The current just was seen at a membrane potential of −70 mV and was activated fully at −140 mV. The voltage value of half-maximal activation of I h was −78.0 ± 6.0 (SE) mV. The rate of I h activation was best approximated by a single exponential function with a time constant that was voltage dependent, ranging from 276 ± 27 ms at −100 mV to 186 ± 11 ms at −140 mV. Reversal potential ( E h) of I h current was more positive than the resting potential. Raising the extracellular potassium concentration shifted E h to a more depolarized value, whereas lowering the extracellular sodium concentration shifted E h in a more negative direction. I h was sensitive to extracellular cesium but relatively insensitive to extracellular barium. The current amplitude near maximal-activation (about −140 mV) was reduced to 40% of control by 1 mM cesium but was reduced to only 71% of control by 2 mM barium. When the membrane potential was near the resting potential (about −60 mV), cesium had no effect on the membrane potential, current-evoked firing rate and input resistance but reduced the spontaneous firing. When the membrane potential was more negative than −70 mV, cesium hyperpolarized the cell, decreased current-evoked firing and increased the input resistance. I h in DNLL neurons does not contribute to the normal resting potential but may enhance the extent of excitation, thereby making the DNLL a consistently powerful inhibitory source to upper levels of the auditory system.


2011 ◽  
Vol 138 (1) ◽  
pp. 95-116 ◽  
Author(s):  
James A. Fraser ◽  
Christopher L.-H. Huang ◽  
Thomas H. Pedersen

Activation of skeletal muscle fibers requires rapid sarcolemmal action potential (AP) conduction to ensure uniform excitation along the fiber length, as well as successful tubular excitation to initiate excitation–contraction coupling. In our companion paper in this issue, Pedersen et al. (2011. J. Gen. Physiol. doi:10.1085/jgp.201010510) quantify, for subthreshold stimuli, the influence upon both surface conduction velocity and tubular (t)-system excitation of the large changes in resting membrane conductance (GM) that occur during repetitive AP firing. The present work extends the analysis by developing a multi-compartment modification of the charge–difference model of Fraser and Huang to provide a quantitative description of the conduction velocity of actively propagated APs; the influence of voltage-gated ion channels within the t-system; the influence of t-system APs on ionic homeostasis within the t-system; the influence of t-system ion concentration changes on membrane potentials; and the influence of Phase I and Phase II GM changes on these relationships. Passive conduction properties of the novel model agreed with established linear circuit analysis and previous experimental results, while key simulations of AP firing were tested against focused experimental microelectrode measurements of membrane potential. This study thereby first quantified the effects of the t-system luminal resistance and voltage-gated Na+ channel density on surface AP propagation and the resultant electrical response of the t-system. Second, it demonstrated the influence of GM changes during repetitive AP firing upon surface and t-system excitability. Third, it showed that significant K+ accumulation occurs within the t-system during repetitive AP firing and produces a baseline depolarization of the surface membrane potential. Finally, it indicated that GM changes during repetitive AP firing significantly influence both t-system K+ accumulation and its influence on the resting membrane potential. Thus, the present study emerges with a quantitative description of the changes in membrane potential, excitability, and t-system ionic homeostasis that occur during repetitive AP firing in skeletal muscle.


1980 ◽  
Vol 58 (9) ◽  
pp. 999-1010 ◽  
Author(s):  
Peter C. Vaughan ◽  
James G. McLarnon ◽  
Donald D. F. Loo

Three-microelectrode voltage-clamp experiments have been conducted on surface fibres of Xenopus laevis sartorius muscles. When potassium and chloride were substituted by rubidium and sulphate, negligibly small currents were observed. In solutions containing rubidium and chloride at pH 8.4–8.8 normally polarized fibres exhibited instantaneous current–voltage relations that were linear over a wide voltage range. Chloride conductance varied widely from fibre to fibre; the mean resting conductance at −80 mV was 7.4 × 10−4 ± 2.6 × 10−4 S/cm2 (mean ± SE). When hyperpolarizing voltage steps were made, conductance declined from the initial to the steady state; inward currents saturated near 14 μA/cm2. In experiments performed on fibres depolarized by immersion in K+-and Rb+-rich solutions it was found that resting conductance did not increase by as much as would be expected from constant field – constant permeability precepts, by comparison with normally polarized fibres. Despite the low chloride transmembrane concentration ratio, rectification in the steady state was similar in depolarized and normally polarized fibres.When a two-pulse protocol was employed to test the availability of chloride conductance after conditioning of the system at some voltage, it was found that the test current, the initial current at the onset of the test voltage step, depended sigmoidally on the conditioning voltage. The sigmoid relationships had asymptotic limits: after hyperpolarizing conditioning the test current was minimal, after depolarizing conditioning, maximal. Normalized sigmoid relations were superimposable, whether from normally polarized or chronically depolarized cells.When the protocol was repeated using different test potentials and initial currents following a particular conditioning voltage were plotted against the test potential, families of straight lines were obtained. The slopes of the members of these families were dependent on the conditioning voltage: the more negative the conditioning step the lower the slope. The lines projected through a mutual intersection at a voltage slightly more positive than the resting potential. This is interpreted as indicating that there is some voltage, slightly positive with respect to the membrane potential, at which the initial current is independent of the conditioning voltage.It is concluded that the state of the chloride conductance mechanism is a function of the deviation of the membrane from the resting potential rather than of the absolute membrane potential and that relaxations from initial to steady states reflect properties of the permeation mechanism rather than accumulation or depletion of chloride in a confined space, although some contribution by a mechanism such as the latter cannot be completely ruled out.


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