Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 3 Na/Ca exchanger in the transverse tubular wall is modelled as the coupling mechanism between transverse tubular depolarization and Ca release from the sarcoplasmic reticulum. At rest, the Ca-occupied site faces the transverse tubular lumen. Upon depolarization, the difference in chemical potentials of Na and Ca gives a net inward force on Ca resulting in a reorientation of the exchanger so the Ca site now faces the myoplasm and releases Ca to stimulate Ca-induced Ca release from the sarcoplasmic reticulum. The rotation of the exchanger's asymmetrical charge could generate the 'charge movement' signal. As depolarization continues, the site is depleted of Ca and contraction ends spontaneously. Repolarization reorients the exchanger; the depleted Ca site now faces the transverse tubular lumen and slowly refills with Ca (repriming). A kinetic model is capable of controlling both twitch and contracture tension. The Na/Ca exchange blocker dichlorobenzamil (Merck) (10 microM), elevated external Na and low pH all slowed the rate of rise of potassium contracture tension. The ratios of rates of tension rise were dCB/control = 0.4 +/- 0.1, elevated external Na/Tris = 0.6 +/- 0.1, pH 6.3/control = 0.7 +/- 0.01. These results can be mimicked with the kinetic model by slowing the rate of 'rotation' (and hence charge movement) by 50%. Elevated internal Na increases the rate of rise of contracture tension; elevated internal Na/control 1.6 +/- 0.3. Dichlorobenzamil also slows the recovery following spontaneous relaxation; the time constant (68 s) of repriming is unchanged but shifted to longer recovery times. Reduced external Na and pH 6.3 also slow recovery in a similar manner, consistent with delayed rotation of the Ca-depleted site. These results suggest that Na/Ca exchange is a step in both the excitation contraction coupling chain and the repolarization-repriming sequence.
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PMID:Na/Ca exchange and excitation--contraction coupling in frog fast fibres. 321 96

The three-dimensional morphology of the surface of myelinated nerve fibres in the mouse sciatic nerve was studied by scanning electron microscopy after combined potassium hydroxide treatment and collagenase digestion (to remove the surrounding collagen fibrils and basal laminae from nerve fibres) as well as by transmission electron microscopy. The myelinated nerve fibre appeared as a long cylinder with sporadic annular constrictions corresponding to the nodes of Ranvier. Slight swellings of the surface due to Schwann cell nuclei were usually found at the middle of each internode. The surface of the nerve fibre clearly exhibited a network of bulges, which consisted of longitudinal bands extending from the nuclear swelling to the nodes of Ranvier through the internode, and transverse trabeculae bridging between these longitudinal bands. These bulges on the surface of nerve fibres were the site of the retained Schwann cell cytoplasm external to the myelin lamellae. These cytoplasmic networks on myelinated fibres presumably corresponded to the networks described by Cajal following silver impregnation. In addition, other thin elevations and focal round swellings were also found associated with these longitudinal bands and transverse trabeculae. These networks of Schwann cell cytoplasm are considered to be cytoplasmic channels for nutrition. The two apposing paranodal bulbs of nodes of Ranvier were often asymmetrical in their structure. The networks of the paranodal region were more complicated than those in the internode. The networks of Schwann cell cytoplasm converged into a continuous circumferential collar toward the node, which in turn gave rise to finger-like projections into the nodal gap.
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PMID:Scanning electron microscopic studies of the myelinated nerve fibres of the mouse sciatic nerve with special reference to the Schwann cell cytoplasmic network external to the myelin sheath. 345 Jul 86

42K+ tracer flux and steady-state conductance measurements were carried out with bilayer lipid membranes containing grisorixin, a carboxylic polyether antibiotic. When the membranes are placed between two bulk aqueous solutions of identical composition, the exchange or self-diffusion transmembrane flux of potassium is measured by a method which allows the characterization of the bilayer K+ permeability at the equilibrium state. The K+ self-diffusion flux increases with the pH in the range pH 6 to pH 9 and reaches a constant value for values above 9. This can be directly related to the increase of the surface concentration of the 1:1 complex formed by K+ and the deprotonated polyether at both bilayer membrane interfaces. The transport model initially proposed by Pressman and co-workers (Proc. Natl. Acad. Sci. USA 58:1949-1956, 1967) is again taken into consideration in the quantitative analysis of the flux data. The transmembrane transport of K+ results from the translocation of its neutral complex with grisorixin and the association-dissociation of the antibiotic with either potassium or protons taking place at both interfacial space layers while the turnover of the mobile carrier is accomplished under asymmetrical conditions by a translocation process of the acidic grisorixin. Using the data of some previous studies for mixed ionophore-lipid monolayers at the air/water interface and the present results for the self-diffusion flux measurements, it was possible to propose an evaluation of the more important parameters characterizing the transport; namely, the total surface concentration of grisorixin, the interfacial pK and the translocation rate constant of its potassium neutral complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transport of potassium ions across planar lipid membranes by the antibiotic, grisorixin: I. The equilibrium state and self-diffusion K+ fluxes. 409 53

1. Asymmetries in the early time course of the displacement current passing across the membrane after application of equal voltage-clamp pulses in the two directions have been investigated in the squid giant axon. Before making the measurements, Na current was blocked by removal of external Na and treatment with tetrodotoxin. Potassium current was usually blocked by perfusion with CsF, but some experiments were done with intact axons. A signal averaging technique was used to eliminate the symmetrical components of the membrane current.2. The asymmetrical current had a contribution of appreciable size attributed to the movement of mobile charges or dipoles in the membrane. This was manifested as an outward current rising rapidly to a peak on depolarization of the membrane and then declining exponentially to zero, followed at the end of the pulse by an inward surge of current with a similar time course. There was also a sustained flow of current outwards during the pulse, arising from ionic leakage with a rectifying characteristic.3. The identification of the exponentially changing current component with the displacement of charged particles forming an integral part of the membrane was supported by the demonstration that the total transfer of charge was equal and opposite at the beginning and end of the pulse, that it reached saturation when the internal potential was taken to a sufficient positive value, and that its size was unaffected by temperature, although its time constant had a large temperature coefficient.4. The disposition of the mobile charges in the steady state was shown to obey a Boltzmann distribution. At the midpoint of the distribution curve, the proportion of the charge displaced underwent an e-fold change for a 19 mV change in potential. The effective valency of the particles, that is their actual charge multiplied by the fraction of the electric field acting on them, was therefore 1.3.5. The total quantity of mobile charge was estimated as about 1500 x 10(-12) C for 0.05 cm(2) of membrane, corresponding to some 1900 charges/mum(2).6. The identification of these mobile charges with the gating particles responsible for controlling Na conductance was supported by the findings that (a) their time constants were the same as those of Hodgkin & Huxley's ;m' system, both in absolute magnitude and in their dependence on potential and temperature, (b) the transition potential at which the charges were evenly distributed on the two sides of the membrane also agreed with that for the ;m' system in intact axons, and its value was similarly shifted in a positive direction by a reduction in internal ionic strength or by raising the external Ca concentration, (c) comparison of the steepness of the curves governing on the one hand the steady-state distribution of the mobile charges and on the other the Na conductance, suggested that an effective cooperation of the charges in groups of three was involved, again in excellent agreement with the ;m' system.7. Displacement of the mobile charges was unaffected by external pH over the range 5-8, but preliminary observations showed that 1% procaine reduced the total charge transfer to somewhat less than 40% of the initial value, and roughly halved the time constant.
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PMID:Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon. 441 38

1. Mechanisms of ion transport across the choroidal epithelium were investigated using an in vitro preparation of the frog choroid plexus.2. Sodium was actively transported across the plexus from the vascular to the ventricular surface by an ouabain sensitive electrically silent pump. As in other epithelial membranes the rate of sodium transport was stimulated by the presence of bicarbonate ions in the Ringer solutions. Chloride and bicarbonate ions accompany the net flux of sodium across this tissue.3. Some experiments suggest that potassium is actively transported from the ventricular to the serosal surface, and that the rate of transport is a function of the extracellular potassium concentration.4. No evidence was obtained to suggest that calcium is actively transported across this tissue in either direction.5. Diamox, ethoxyzolamide, pitocin, pitressin, hydrocortisone, amiloride, spironolactone and anoxia all failed to influence sodium transport.6. The sequence of passive ion permeation across the plexus was P(Rb) approximately P(K) > P(Cs) approximately P(Na) approximately P(Cl) approximately P(HCO3) > P(Li) as deduced from diffusion potential measurements. At least for Na, K and Cl there was a good correlation between the permeability coefficients derived from unidirectional flux measurements and from electrical parameters. This indicates that exchange diffusion is unimportant as a mechanism for passive ion transport.7. The instantaneous current-voltage curves were linear in both symmetrical and asymmetrical salt solutions and the choroid plexus conductance was found to be directly proportional to the external salt concentration. These and other lines of evidence suggest that the major route of passive ion permeation across this epithelium is via the tight junction route and not through the cell interior.8. These results are discussed in relation to the in vivo studies of c.s.f. secretion and the mechanisms of active and passive ion transport across other epithelial membranes such as the gall-bladder, intestine and renal proximal tubule.
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PMID:Mechanisms of ion transport across the choroid plexus. 453 45

Myelinated axons were isolated from the sciatic nerve of Xenopus laevis and were subjected to localized (less than 30 microns wide) lesions. In axons which were bathed in a 0.12 M potassium glutamate solution there was very little local reaction to the lesion and optically-detectable particles undergoing axoplasmic transport accumulated immediately adjacent to, and mostly distal to, the lesion. Preparations fixed for electron microscopy at times up to 3 h following the lesion showed that the axoplasmic changes about the lesion were asymmetrical. Large organelles predominated on the distal side of the lesion; these were mostly dense lamellar bodies (DLB) with mean dimensions, as determined from thin sections, of 0.48 by 0.19 microns. Multivesicular bodies, mitochondria, and a variety of smaller membrane bounded bodies also appeared in the particle accumulation distal to the lesion. Analysis of these results led to the conclusion that DLB were transported up to the lesion and represent the majority of the optically detectable particles which are transported in the retrograde direction. Small vesicles and tubules were the commonest structures which accumulated proximal to the lesion. The time course of this accumulation was consistent with the hypothesis that these structures are particulate bodies which move in the orthograde direction at about 1.5 microns/s. Incidental findings which are also of significance to the study of axonal transport were: large particulate material may reverse its direction of movement at an axonal obstruction, and organelles which accumulate on either side of a lesion do so in rows which are associated with microtubules.
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PMID:The short term accumulation of axonally transported organelles in the region of localized lesions of single myelinated axons. 616 22

The effect of severe zinc deficiency on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper and manganese) in brain regions (olfactory lobes, right and left hippocampi, cerebellum and the rest of the brain) has been studied. After male rats (30 days old) were fed a zinc-deficient diet for 28 days, the zinc concentration of most brain parts was similar to zinc-adequate control values. Olfactory lobe zinc, on the other hand, was slightly depressed. However, the levels of other metals were dependent on zinc nutriture. Zinc deficiency caused an elevation in copper concentrations in most brain parts. Restriction of food intake caused a similar increase in brain copper but generally the effect was less than with zinc deficiency. Levels of calcium, manganese, sodium and potassium, in certain brain regions, also appeared to be altered by the zinc status of an animal. Of the minerals examined, only zinc and copper displayed asymmetrical distribution between the right and left hippocampus, and severe zinc deficiency did not affect lateral distribution of these trace metals in the hippocampus. The data suggest the hypothesis that changes in brain metal content, associated with zinc deficiency, contribute to the behavioral abnormalities that occur.
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PMID:Severe zinc deficiency: effects on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper and manganese) in regions of the rat brain. 661 70

Oxygen tension differences across the mouse ear have been measured polarographically under conditions of no blood flow. For some experiments the ear was split into two by cleavage along the central cartilage plate, and the diffusion of oxygen measured in both directions across these asymmetrical preparations. Measurements were also made on ears from which the stratum corneum had been removed by stripping with Sellotape. It was possible to relate these results to a simple multi-layer diffusion model. The main barrier to diffusion of oxygen resides in the stratum corneum, whose permeability is estimated to be 1 . 2 X 10(-8) ml O2 atm-1 cm-1 S-1. The permeability of the rest of the ear is 4 . 7 X 10(-7) ml O2 atm-1 cm-1 S-1. The inhibition of tissue respiration by the local injection of solutions of sodium amytal, potassium cyanide and other substances reduced the oxygen gradients by factors of between 3 and 7. Cooling the ear from room temperature to 0 degree C reduced the gradients by a factor of about 4.
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PMID:Diffusion of oxygen through the mouse ear. 725 78

It is generally assumed that noises have a detrimental effect when the cochlear receptor is overloaded and, more specifically, when the cochlear microphonic (CM) fails to increase linearly with intensity. In order to investigate further the relations between the nonlinearity of CM and damage to the cochlea, a series of experiments was carried out on guinea pigs to relate the short-term CM depression following the presentation of noises or tones with the nonlinearity and the assymmetry. The asymmetrical non-linearity of CM was measured in tracing the input-out functions and also the wave-forms. Two other important tests of the asymmetrical nonlinearity were used: the measure of interference and of summating potential (SP DIF). The results show that the fatigability is greater when there is a large negative asymmetry or a large negative SP. Variations in asymmetry and in SP were observed among individuals. Other changes of symmetry were provoked by asphyxia or by introducing solutions of KCl in the perilymph. These changes were well correlated with the fatigability. These results are interpreted in a model of the cochlear transducer derived from the model of Davis. The assymetry of a flux of potassium ions between endolymph and the hair cells is assumed to be responsible for the alterations associated with cochlear fatigue and trauma.
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PMID:Relations between cochlear fatigue and the asymmetrical nonlinearity of the cochlear microphonics. 736 35

To determine how voltage-gated ion channels segregate between sibling cells at cytokinesis, we used a whole-cell patch clamp to measure the electrophysiological phenotypes of siblings within 45 min of division. Recently born siblings in an immortalized line of embryonic retinal cells were identified as pairs of spherical cells adhering to one another. All siblings were electrically coupled when cells were simultaneously voltage clamped, whereas nonsiblings were not coupled. Twelve pairs of siblings were electrically isolated by mechanical separation so that their phenotypes could be measured independently. Cells expressed two principal membrane conductances, delayed rectifier-like (IK) and inward rectifier (IK(IR)) potassium currents. Despite qualitative and quantitative variability in IK and IK(IR) expression within the population, each cell of a given pair expressed similar steady-state current densities between -110 and +50 mV. We estimated IK(IR) slope conductance by blocking the current specifically with 5 mM Cs and calculated IK(IR) ratios in siblings and nonsiblings. Three pairs of siblings expressed IK(IR) ratios of approximately 1.2, while ratios in three pairs of adhered nonsiblings varied between 1.6 and 5.4. When currents were sampled continuously through cytokinesis by using the perforated-patch recording mode, current amplitude showed no net change within 30 min of division. Because channel number did not appear to change in siblings during this interval, parental channels were inherited by each daughter in proportion to the area of membrane received. Heterogeneity therefore arises after siblings reenter interphase and is not due to the asymmetrical segregation of channels at cytokinesis.
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PMID:Symmetrical segregation of potassium channels at cytokinesis. 768 65


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