Changes In Potassium Permeability Research Articles

In skeletal muscle the relaxation of the resting membrane potential induced by K(+) permeability changes depends on Cl(-) transport.

In resting skeletal muscle the potassium permeability is determined by the permeability of the inwardly potassium rectifier. Continuous resting membrane potential measurements are done to follow the relaxation of the membrane potential upon changes in potassium permeability. Inhibition of the inwardly potassium rectifier, by extracellular application of 80 microM Ba(2+), causes the cell to depolarize with mean time constants as follows: in control 127+/-7 s ( n=23), in the presence of bumetanide, as an inhibitor of the Na(+)/K(+)/2Cl(-) cotransporter, 182+/-23 s ( n=7), in hypertonic media (340 mosmol/kg) 90.4+/-5 s ( n=7) and in reduced chloride medium 64+/-8 s ( n=5). The depolarizing relaxation of the membrane potential induced by reduction of extracellular potassium produces similar results. These time constants are at least three orders of magnitude slower than the time constants reported in the literature for the inhibition of the inwardly potassium rectifier. Chloride transport affects the relaxation of the membrane potential. A further characterization of chloride transport is done by following the relaxation of the membrane potential upon application of chloride transport modulators. It is argued that the electroneutral cotransporter, for which a flux was preliminarily estimated of 13.4 pmol cm(-2) s(-1), has a considerable role in the processes related to the resting membrane potential.

Developmental changes in blood‐brain barrier potassium permeability in the rat: relation to brain growth.

1. The potassium permeability of the blood-brain barrier (BBB) was determined in anaesthetized rats aged between 21 days gestation and adult using 86Rb+ as a marker for potassium. 2. The brain influx rate constant for 86Rb+ was high in fetal cortex at 21 days gestation (42.5 +/- 4.3 microliters g-1 min-1) but had decreased markedly by just after birth (12.2 +/- 0.6 microliters g-1 min-1). There was a further, gradual, postnatal decline to 7.0 +/- 0.3 microliters g-1 min-1 by 50 days after birth. 3. Developmental changes in passive BBB permeability were examined over the same age range using 14[C]urea. These studies showed similar developmental changes in influx rate to those found for 86Rb+. Specifically, a marked perinatal decline followed by a more gradual postnatal fall. Thus, the changes in potassium permeability probably reflect a decrease in the BBB paracellular leak during development. 4. The changes in BBB permeability coincide with changes in the rate of brain growth and the associated rate of brain potassium accumulation. As the potassium permeability properties of the adult BBB would provide insufficient potassium influx to meet the requirement associated with fetal brain growth, it is suggested that need for potassium may be the reason for the greater BBB permeability early in development.

4‐Aminopyridine interrupts the modulation of acetylcholine release mediated by muscarinic and opiate receptors

The effect of 4-aminopyridine, a potassium channel blocker on the muscarinic and opiate modulation of acetylcholine release, was investigated. Rat frontal cortical slices were loaded with [3H]choline, superfused continuously, and stimulated electrically. 4-Aminopyridine enhanced the stimulation-evoked release of tritium without affecting basal release. The electrically evoked release of radioactivity was reduced by the muscarinic agonist oxotremorine and the delta selective opiate receptor agonist Metenkephalin, and was enhanced in the presence of the cholinesterase inhibitor physostigmine by the muscarinic antagonist atropine. These effects were completely abolished by 4-aminopyridine. Since 4-aminopyridine blocks potassium permeability of the neuron, it is suggested that the changes in potassium permeability and the consequent alteration of membrane polarization are involved in the presynaptic modulation of acetylcholine release.

Involvement of a cytoplasmic protein in calcium-dependent potassium efflux in red blood cells.

The potassium permeability of the human red blood cell increases with the free intracellular calcium concentration. The efflux of potassium can be inhibited by iodoacetic acid. This inhibitory effect correlates directly with the carboxymethylation of a protein band found in both the hemolysate and membrane fractions. The present study provides two additional lines of evidence that this protein is involved directly with the calcium-dependent changes in potassium permeability: its association with the membrane is calcium dependent; and calcium-dependent potassium efflux from resealed ghost is inhibited by the incorporation of antibodies raised against this cytoplasmic protein.

Dependence on calcium of potassium- and agonist-induced changes in potassium permeability of rabbit ear artery.

The effect of K+ depolarization and agonists on the 86Rb+ efflux from rabbit ear artery has been investigated. K+ depolarization with 59 mM-K+ induces an increase of the 86Rb+ efflux rate, which is dependent on [Ca2+]o and is correlated with the concomitant force development. This effect is largely reduced by Ca2+ antagonists, such as D-600 and Mn2+. The residual increase of the 86Rb+ efflux rate is much smaller than that predicted by the constant-field equations. Stimulation with 10(-5) M-noradrenaline or 10(-4) M-histamine induces a biphasic increase of the efflux rate. The initial transient effect is reduced in low [Ca2+]o solutions, whereas the maintained component is largely independent of [Ca2+]o. Stimulation with noradrenaline during depolarization of the tissues with K+ induces, after a transient increase of the efflux rate, an inhibition of the K+-induced increase of the efflux rate. Both phases of the noradrenaline action are due to activation of alpha-adrenoreceptors. Exposure to Ca2+-free medium induces a progressive increase of the 86Rb+ efflux rate, which reaches a new steady-state value after about 60 min. Stimulation with noradrenaline after this 60 min exposure to Ca2+-free solution no longer induces a significant effect. Stimulation with noradrenaline after shorter exposures to Ca2+-free solution immediately increases the 86Rb+ efflux to a value close to the steady-state value obtained after prolonged exposure to Ca2+-free medium. Washing out the agonist has no effect on the rate constant. It will only return to its control value after exposure to solutions containing Ca2+. This recovery of the rate constant by external Ca2+ also occurs in the presence of 1 mM-Mn2+ in the perfusion fluid. On re-exposure of the tissues in the presence of 1 mM-Mn2+ to Ca2+-free solution the rate constant of the 86Rb+ efflux increases at once to the steady-state value observed in Ca2+-free solution. This increase proceeds gradually if the tissues have been re-exposed in the absence of Mn2+. It is concluded that K+ permeability might be regulated by [Ca2+]i and that this relationship can be affected by agonists. In order to explain the effects of Ca2+-free medium on the 86Rb+ efflux we have to assume that at very low values of [Ca2+]o and [Ca2+]i the membrane permeability for K+ is modified by a different mechanism.

Changes in potassium permeability and membrane potential of bovine red blood cells estimated by the use of a dimerizing fluorescence probe.

The partition of 3, 3'-dipropyl-2, 2'-thiadicarbocyanine, diS-C3 (5), between the i terior of bovine red cells and bulk aqucous medium was measured by using fluorescence spectroscopy. Inside the cells (concentrated hemoglobin phase), diS-C3 (5) is intensely concentrated and consequently forms the nonfluorescent dimer. Valinomycin stimulates K+ transport across the cell membrane and the resulting change in membrane potential induces an alteration of the partitioning and the dimerization of diS-C3 (5). The changes in membrane potential and permeability of the red cell membrane to K+ were quantitatively associated with this dimerizatioo. The permeability of the membrane to K+ estimated here can be correlated with the characteristic properties of bovine red cell membrane, that is, the high content of sphingomyelin and the rigidity of this membrane.

Functional importance of sodium and potassium in the guinea pig cochlea studied with amiloride and tetraethylammonium.

The effects of amiloride on the cochlear responses in the guinea pig were compared with those produced by tetraethylammonium (TEA). Amiloride has been reported to reduce membrane permeability to sodium in a wide variety of ion-transporting epithelia. TEA has been documented to suppress the active potassium permeability increase during the repolarization phase of the action potential in mammalian excitable cells, and to reduce the resting potassium conductance in mammalian smooth muscle cells. Perilymphatic perfusion of 10(-3) M amiloride or intravenous injection at a dose of 20 mg/kg suppressed the whole nerve action potential (AP) of the cochlea but did not significantly affect the cochlear microphonics (CM) or endocochlear potential (EP). Application of amiloride to endolymph by iontophoretic or perfusion techniques also produced no significant changes of CM and EP when compared with appropriate control procedures. Perilymphatic perfusion of 10(-2) M TEA did not suppress CM or EP but the AP was reduced. Iontophoretic application of TEA to the endolymph caused a marked suppression of CM while the EP was significantly increased. The effects of endolymphatic TEA application are consistent with the concept that the normal EP recorded from scala media is the algebraic sum of a positive electrogenic potential and a negative diffusion potential, the latter component being sensitive to potassium permeability changes of the endolymph-perilymph barrier. Maintenance of normal cochlear microphonics also appears dependent upon the maintenance of normal potassium permeability properties of the endolymph-perilymph barrier. The functional importance of normal sodium permeability properties appears less certain.

Glucose-induced electrical activity in the pancreatic beta-cell: effect of veratridine.

Veratridine was used in the presence of glucose to assess the role of the Na pump in the regulation of glucose-induced burst activity. In the presence of 8.4 mM glucose, veratridine elicited a silent hyperpolarization, followed by burst activity. The magnitude of depolarization to plateau potential and the duration of the silent phase were increased. The addition of tetrodotoxin (TTX) restored the pattern of electrical activity to that observed in the absence of veratridine. Similar results were observed when veratridine was used in the presence of 16.7 mM glucose and tetraethylammonium (blocks voltage-dependent potassium permeability). TTX or ouabain blocked the effects of veratridine, and produced depolarization and continuous spike activity. Quinine (blocks Ca-dependent potassium permeability) elicited continuous spike activity in the presence of 16.7 mM glucose. The addition of veratridine induced only a transient return to burst activity, followed by a return to continuous spike activity. These results suggest that an electrogenic Na pump is an important factor in maintaining the transmembrane potential at an optimum level for operation of a voltage- and Ca-sensitive potassium permeability: changes in potassium permeability operating on a background of electrogenic current may be responsible for the voltage transitions associated with burst activity.

Voltage-dependent potassium channels in the amphibian lens membranes: Evidence from radiotracer and electrical conductance measurements

The electrical potential and conductance of the perfused frog lens preparation was measured using a two internal microelectrode technique. When the lens potential was depolarized by perfusing with high potassium concentration ringer the increase in conductance could not be fitted by conductance equations where P K was assumed constant. It is suggested therefore that this increase is due to a voltage-dependent component of the conductance, namely voltage-dependent potassium channels. Direct evidence for the existence of a voltage-dependent conductance is presented in the form of conductance-voltage curves which show rectification similar to squid axon. Conductance-voltage curves mapped out in high potassium Ringer show a blocking effect of potassium on the lens conductance. The blocking effect was also observed in lenses where the membrane voltage was clamped to a steady value during exposure to high potassium solutions. The increase in conductance at depolarized lens potentials is demonstrated by changes in potassium permeability as measured from the efflux of 42 K. Both the electrical conductance and 42 K efflux are shown to be sensitive to potassium channel blocking agents, namely, tetraethylammonium (TEA), caesium and rubidium ions. The 42 K efflux rate constant and lens potential were monitored simultaneously whilst depolarizing and hyperpolarizing currents were applied and the changes in 42 K efflux clearly demonstrated the voltage-dependence of the potassium permeability.

Contribution of calcium and potassium permeability changes to the off response of scallop hyperpolarizing photoreceptors.

1. The membrane response of the distal photoreceptors in the retina of the scallop Pectin irradians to the termination of a bright white light (off response) is shown to be composed of the decay of the hyperpolarizing receptor potential and an action potential with slow kinetics. 2. The action potential can be produced in darkness in the absence of external Na+ ions by membrane depolarization. 3. The action potential is maintained by replacement of external Ca2+ with Sr2+ or Ba2+, but not by Mg2+. In normal external Ca2+ (9mM), the action potential is abolished by the addition of the Ca2+ inhibitors, La3+, Co2+, and Mn2+ or the organic Ca2+ antagonist D-600. 4. Elevated external Ca2+ concentrations increase the rate of rise and peak amplitude of the action potential as well as the rate of repolarization and after hyperpolarization, but decrease the duration. 5. The rate of rise and peak amplitude of the action potential are increased by the K+ antagonists tetraethylammonium (TEA) 4-amino-phyridine (4-AP), Ba2+ and procaine. The antagonists have different effects on subsequent phases of the response, however. External TEA and Ba2+ increase the duration, but decrease the rate of repolarization and abolish the after hyperpolarization, whereas external 4-AP and procaine increase the rate of repolarization, decrease the duration and increase the after hyperpolarization. 6. The ratio of the Ca2+ to K+ permeability (P Ca/P K) estimated from the constant field equation at the peak of the action potential in different external Ca2+ concentrations is close to 1. 7. The maximum rate of rise and the peak amplitude of the action potential are increased by membrane hyperpolarization and decreased by membrane depolarization. They are decreased by background light intensity relative to their value in the dark. 8. In normal ASW the action potential can be identified during the off response as a small overshoot of membrane potential relative to its value in the dark. 9. The rate of repolarization of the off response in normal ASW is reduced by agents or conditions which inhibit or reduce Ca2+ permeability changes, e.g. external Co2+ and La2+ or zero external Ca2+. 10. Our results suggest that a voltage-dependent increase in membrane permeability to Ca2+ and to K+ ions modifies the repolarizing phase of the receptor potential.

Cation permeability ratios of sodium channels in normal and grayanotoxin-treated squid axon membranes.

Permeabilities of squid axon membranes to various cations at rest and during activity have been measured by voltage clamp before and during internal perfusion of 4 X 10(-5) M grayanotoxin I. The resting sodium and potassium permeabilities were estimated to be 6.85 X 10(-8) cm/sec and 2.84 X 10(-6) cm/sec, respectively. Grayanotoxin I increased the resting sodium permeability to 7.38 10(-7) cm/sec representing an 11-fold increase. The potassium permeability was increased only by a factor of 1.24. The resting permeability ratios as estimated by the voltage clamp method before application of grayanotoxin I were Na (1): Li (0.83): formamidine (1.34): guanidine (1.49): Cs (0.87): methylguanidine (0.86): methylamine (0.78). Grayanotoxin I did not drastically the resting permeability ratios with a result of Na (1): Li (0.95): formamidine (1.27): guanidine (1.16): Cs (0.47): methylguanidine (0.72): methylamine (0.46). The membrane potential method gave essentially the same resting permability ratios before and during application of grayanotoxin I if corrections were made for permeability to choline as the cation substitute and for changes in potassium permeability caused by test cations. The permeability ration choline/Na was estimated to be 0.72 by the voltage clamp method and 0.65 by the membrane potential method. Grayanotoxin I decreased the ration to 0.43. The permeability ratios during peak transient current were estimated to be Na (1): Li (1.12): formamidine (0.20): guanidine (0.20): Cs (0.085): methylguanidine (0.061): methylamine (0.036). Thus the sodium channels for the peak current are much more selective to cation than the resting sodium channels. It appears that the resting sodium channels in normal and grayanotoixn I-treated axons are operationally different from the sodium channels that undergo a conductance increase upon stimulation.

Repetitive impulse firing: comparisons between neurone models based on 'voltage clamp equations' and spinal motoneurones.

AbstractRepetitive impulse firing was elicited in neurone models by steady stimulating currents of abrupt onset. The neurone models were based on the Frankenhaeuser—Huxley equations (1964) for voltage clamp data from the amphibian peripheral nerve. A frequency‐current curve (‘f‐I curve’), initial adaptation, and minimum firing rate similar to those of cat spinal motoneurones were obtained in the Frankenhaeuser—Huxley model if it were provided with (i) a long‐lasting after‐hyperpolarization due to potassium permeability changes, and (ii) a decreased subthreshold sodium inactivation. For detailed comparisons to the repetitive impulse firing of spinal motoneurones, model versions were used in which the subthreshold sodium inactivation was very slight, and the passive membrane properties as well as the afterpotentials resembled those of spinal motoneurones. In their repetitive behaviour, these models were quantitatively similar to spinal motoneurones. In the motoneurone‐like model versions, initial adaptation was due to a kind of ‘summation’ of the potassium permeability changes underlying the after‐hyperpolarizations of consecutive spikes. The slope of the f‐I curve was markedly affected by modifications of the size or time course of the potassium permeability changes responsible for the after‐hyperpolarization.

Motoneurone models based on 'voltage clamp equations' for peripheral nerve.

AbstractMotoneurone models were developed by modifications of the Frankenhaeuser‐Huxley equations (1964) for voltage clamp data amphibian nerve fibre. The major modifications were: (i) that the subthreshold sodium inactivation was decreased, and (ii) that the Frankenhaeuser‐Huxley model was provided with a long‐lasting after‐hyperpolarization due to potassium permeability changes. Besides, model versions were developed that also had passive membrane properties (e. g. a resting membrane time constant) similar to those of spinal motoneurones. For various model versions, single spikes and the associated afterpotentials were shown in the present paper. The main aim was to use the motoneurone models for studies of repetitive impulse firing. This will be done in a subsequent paper (Kernell and Sjoholm 1972).

Slow changes in potassium permeability in skeletal muscle.

1. Voltage clamp experiments on sartorius muscle fibres at 3 degrees C showed that the potassium current is divisible into three components, namely:(a) Current in the delayed rectifier channel, which reached a maximum in about 0.1 sec at -30 mV, and declined with a time constant of about 4 msec when the fibre was repolarized to -100 mV; this component had an approximately linear instantaneous current-voltage relation and an equilibrium potential E(1) at 10-15 mV positive to the resting potential.(b) A slow component which reached a maximum in about 3 sec at -30 mV, and declined with a time constant of about 0.5 sec when the fibre was repolarized to -100 mV; this component had an approximately linear instantaneous current-voltage relation and a mean equilibrium potential E(2) at -83 mV in fibres where E(1) averaged -75 mV.(c) Current in the inward rectifier channel which decreased with a time constant of about 0.25 sec when the fibre was hyperpolarized to -150 mV. This component had an equilibrium potential close to the resting potential and an instantaneous current-voltage relation which was that of an inward rectifier.2. The general characteristics of the late after-potential in muscles in hypertonic solutions at 3 degrees C are consistent with those of the slow conductance change. The sign of the late after-potentials was reversed by depolarizing below -80 mV.3. The decline of current during a maintained hyperpolarization cannot be attributed solely to a decrease in tubular potassium concentration, since there may be a large decrease in current without much alteration of equilibrium potential. The negative slope conductance often seen at -150 mV is also difficult to reconcile with the tubular depletion hypothesis.4. Replacement of 10 mM-K by 10 mM-Rb abolished inward rectification but had less effect on the fast and slow components of the potassium conductance.

THE EFFECT OF TEMPERATURE ON THE SODIUM AND POTASSIUM PERMEABILITY CHANGES IN MYELINATED NERVE FIBRES OF XENOPUS LAEVIS.

The Journal of PhysiologyVolume 169, Issue 2 p. 431-437 ArticleFree Access The effect of temperature on the sodium and potassium permeability changes in myelinated nerve fibres of Xenopus laevis B. Frankenhaeuser, B. FrankenhaeuserSearch for more papers by this authorL. E. Moore, L. E. MooreSearch for more papers by this author B. Frankenhaeuser, B. FrankenhaeuserSearch for more papers by this authorL. E. Moore, L. E. MooreSearch for more papers by this author First published: 01 November 1963 https://doi.org/10.1113/jphysiol.1963.sp007269Citations: 175AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume169, Issue2November 1, 1963Pages 431-437 RelatedInformation