The propagation potential. An axonal response with implications for scalp-recorded EEG

An electrophysiological response of axons, referred to as the "propagation potential," was investigated. The propagation potential is a sustained voltage that lasts as long as an action potential propagates between two widely spaced electrodes. The sign of the potential depends on the direction of action potential propagation. The electrode towards which the action potential is propagating is positive with respect to the electrode from which it is receding. For normal frog sciatic nerves the magnitude of the propagation potential was 17% of the peak of the extracellular action potential; TEA increased it to 32%. For normal earthworm median or lateral giant fibers it was 30%. A ripple pattern on the propagation potential was attributed to variation in resistance along the length of the worm. Cooling increased the duration of the propagation potential and attenuated the higher frequency components of the ripple pattern. Differential records from two widely spaced intracellular microelectrodes in the same axon differed from the propagation potential. The amplitude of the plateau relative to the peak was smaller, it decreased as the action potential propagated from one electrode site to the other, and the potential did not return to zero as rapidly as for extracellular records. When propagation was blocked by heat, the propagation potential slowly decayed. There was no ripple pattern during the decay. In a volume conductor, electrodes contacting the worm did not show the typical propagation potential, but electrodes located a few centimeters away from the worm did. Simple core-conductor models based on classical action potential theory did not reproduce the propagation potential. More complex, modified core-conductor models were needed to accurately simulate it. The results suggest that long, slowly conducting fibers can contribute to the scalp-recorded EEG.     

A 13C NMR approach to categorizing potential limitations of alpha,beta-unsaturated carbonyl systems in drug-like molecules

Compounds that contain an alpha,beta-unsaturated carbonyl moiety are often flagged as potential Michael acceptors. All alpha,beta-unsaturated carbonyl moieties are not equivalent, however, and we sought to better understand this system and its potential implications in drug-like molecules. Measurement of the (13)C NMR shift of the beta-carbon and correlation to in vitro results allowed compounds in our collection to be categorized as potential Michael acceptors, potential substrates for NADPH, or as photoisomerizable.     

Increase in lipid microviscosity of unilamellar vesicles upon the creation of transmembrane potential

Summary Diffusion potential of potassium ions was formed in unilamellar vesicles of phosphatidyl choline. The vesicles, which included potassium sulfate buffered with potassium phosphate, were diluted into an analogous salt solution made of sodium sulfate and sodium phosphate. The diffusion potential was created by the addition of the potassium-ionophore, valinomycin. The change in lipid microviscosity, ensuing the formation of membrane potential, was measured by the conventional method of fluorescence depolarization with 1,6-diphenyl-1,3,5-hexatriene as a probe. Lipid microviscosity was found to increase with membrane potential in a nonlinear manner, irrespective of the potential direction. Two tentative interpretations are proposed for this observation. The first assumes that the membrane potential imposes an energy barrier on the lipid flow which can be treated in terms of Boltzmann-distribution. The other interpretation assumes a decrease in lipid-free volume due to the pressure induced by the electrical potential. Since increase in lipid viscosity can reduce lateral and rotational motions, as well as increase exposure of functional membrane proteins, physiological effects induced by transmembrane potential could be associated with such dynamic changes.     

A distance-dependent atomic knowledge-based potential for improved protein structure selection.

A heavy atom distance-dependent knowledge-based pairwise potential has been developed. This statistical potential is first evaluated and optimized with the native structure z-scores from gapless threading. The potential is then used to recognize the native and near-native structures from both published decoy test sets, as well as decoys obtained from our group's protein structure prediction program. In the gapless threading test, there is an average z-score improvement of 4 units in the optimized atomic potential over the residue-based quasichemical potential. Examination of the z-scores for individual pairwise distance shells indicates that the specificity for the native protein structure is greatest at pairwise distances of 3.5-6.5 A, i.e., in the first solvation shell. On applying the current atomic potential to test sets obtained from the web, composed of native protein and decoy structures, the current generation of the potential performs better than residue-based potentials as well as the other published atomic potentials in the task of selecting native and near-native structures. This newly developed potential is also applied to structures of varying quality generated by our group's protein structure prediction program. The current atomic potential tends to pick lower RMSD structures than do residue-based contact potentials. In particular, this atomic pairwise interaction potential has better selectivity especially for near-native structures. As such, it can be used to select near-native folds generated by structure prediction algorithms as well as for protein structure refinement.     

Activation of phospholipase C increases intramembrane electric fields in N1E-115 neuroblastoma cells

We imaged the intramembrane potential (a combination of transmembrane, surface, and dipole potential) on N1E-115 neuroblastoma cells with a voltage-sensitive dye. After activation of the B(2) bradykinin receptor, the electric field sensed by the dye increased by an amount equivalent to a depolarization of 83 mV. The increase in intramembrane potential was blocked by the phospholipase C (PLC) inhibitors U-73122 and neomycin, and was invariably accompanied by a transient rise of [Ca(2+)](i). A depolarized inner surface potential, as the membrane loses negative charges via phosphatidylinositol 4,5-bisphosphate (PIP(2)) hydrolysis, and an increase in the dipole potential, as PIP(2) is hydrolyzed to 1,2-diacylglycerol (DAG), can each account for a small portion of the change in intramembrane potential. The primary contribution to the measured change in intramembrane potential may arise from an increased dipole potential, as DAG molecules are generated from hydrolysis of other phospholipids. We found bradykinin produced an inhibition of a M-type voltage-dependent K(+) current (I(K(M))). This inhibition was also blocked by the PLC inhibitors and had similar kinetics as the bradykinin-induced modulation of intramembrane potential. Our results suggest that the change in the local intramembrane potential induced by bradykinin may play a role in mediating the I(K(M)) inhibition.     

Effects of Extended Periods of Osmotic Stress on Water Relationships of Pepper

Pepper plants grown to uniform size in a controlled environment were subjected to an osmotic stress for periods of 1 to 10 days. Polyethylene glycol 400 was used as the osmotic agent. Leaf area of the plants, grown under uniform conditions, was proportional to the weight of the plants. This relationship was not altered by reduction in rate of growth due to a decrease in osmotic potential of the nutrient solution. The rate of transpiration of the pepper plants decreased as the osmotic potential of the nutrient solution was decreased. The reduction in rate of transpiration was most rapid when the osmotic potential was reduced from ?0.5 to ?7.5 bars. There was continued reduction in the rate of transpiration with change in potential to ?12.5 bar but this change was less than that at the higher potentials. The rate of transpiration remained at a reduced rate for as long as the plants were growing in the solution with low osmotic potential. Alternating the osmotic potential of the nutrient solution between ?0.5 and ?5.0 bar did not change the response to the ?5.0 tension. The reduction in rate of transpiration resulting from the lowering of the osmotic potential by addition of NaCl was similar to that produced by addition of polyethylene glycol. Water potential, osmotic potential, relative water content and stomatal movement were all in dynamic equilibrium with the water content of the leaves. The water content of the leaves was regulated by the supply and demand. In these investigations the demand remained constant. The supply was altered by decreasing the difference in water potential between leaf and substrate and by an increase in resistance to flow of water in the roots as a result of the decrease in osmotic potential of the nutrient solution.     

Effects of external currents on duration and amplitude of normal and prolonged action potentials from single nodes of Ranvier

Duration and amplitude of normal and prolonged action potentials from single nodes of Ranvier vary as functions of potential changes induced by currents from an external source. The quantitative relations between externally applied potential and the resulting potential generated within the system are analyzed in order to obtain information about the kinetics of the electromotance,—potential,—and chemical changes taking place during excitation. The following preliminary conclusions are drawn: A depolarizing and a repolarizing process (positive and negative electromotance) increase and decrease with the potential. For a sudden potential displacement the negative electromotance reaches its new value at a faster rate than the positive electromotance. Since the individual values of the two electromotances depend on the potential and since they both generate a potential which is proportional to the difference of their absolute values, the values of either electromotance are determined by this difference as well as by any externally induced potential change.     

Membrane potential and Donnan potential

The Nernst-Planck-Poisson equations for the potential profile across a membrane are exactly solved without recourse to the assumption of constant field within the membrane. It is assumed that the membrane core of thickness dc is covered by a surface layer of thickness ds in which the membrane-fixed charges are distributed at a uniform density N. The membrane boundary potentials as well as the diffusion potentials contribute to the membrane potential. It is shown that for ds greater or similar 1/k, k being the Debye-Hückel parameter, the potential in the membrane surface layer except in the region very near the membrane/solution boundary is effectively equal to the Donnan potential and that its contribution to the membrane potential becomes dominant as N increases. For low N, on the other hand, the membrane potential arises mostly from the diffusion potential.     

The nature of adaptive evolutionary changes: fitness and potential

Ecological potential of an individual can be defined as its viability in the broad sense including the ability to reproduce in various environments. From the biological viewpoint, ecological potential as a fundamental property of an organism is more important than fitness in the genetic sense, which is estimated as the relative rate of reproduction. In essence, fitness reflects the level of implementation of the biological potential. In the process of evolution, regulatory selection results in an increase of fitness: selected forms reproduce more successfully as the population size increases. By contrast, individuals with high ecological potential are more advantageous when the population size decreases, because the probability of their survival in adverse environments is high. Thus, high levels of fitness and ecological potential are achieved via operation of different types of selection.     

Origin of Axon Membrane Hyperpolarization under Sucrose-Gap

One of the disadvantages of the sucrose-gap method for measuring membrane potentials with extracellular electrodes is a membrane hyperpolarization of the order of 30 to 60 mv, as compared with the resting potential obtained with intracellular microelectrodes in the absence of a sucrose-gap. In the present study the contribution of the sucrose-sea water junction potential to this hyperpolarization effect has been evaluated by comparing the effects on the resting potential of several anion and cation substitutions in the sea water bathing the lobster giant axon under sucrose-gap. Measurements with microelectrodes demonstrate a significant liquid junction potential between sucrose and standard artificial sea water. The value of this liquid junction potential as well as the measured resting membrane potential varies as a function of the anions and cations substituted in the sea water. Both the liquid junction potential and the sucrose-gap-induced hyperpolarization can be eliminated by using a low mobility anion to replace most of the chloride in sea water while the normal cation content remains unchanged. These data provide evidence that loop currents at the sucrose-sea water-axon junctions are at least partly responsible for membrane hyperpolarization under a sucrose gap.     

Application of eukaryotic and prokaryotic laccases in biosensor and biofuel cells: recent advances and electrochemical aspects

Laccases exhibit a wide range of applications, especially in the electrochemical field, where they are regarded as a potential biotic component. Laccase-based biosensors have immense practical applications in the food, environmental, and medical fields. The application of laccases as biocathodes in enzymatic biofuel cells has promising potential in the preparation of implantable equipment. Extensive studies have been directed towards the potential role of fungal laccases as biotic components of electrochemical equipment. In contrast, the potential of prokaryotic laccases in electrochemistry has been not fully understood. However, there has been recent and rapid progress in the discovery and characterization of new types of prokaryotic laccases. In this review, we have comprehensively discussed the application of different sources of laccases as a biocatalytic component in various fields of application. Further, we described the potential of different types of laccases in bioelectrochemical applications.

     

Potential energy barriers to ion transport within lipid bilayers. Studies with tetraphenylborate.

Tetraphenylborate-induced current transients were studied in lipid bilayers formed from bacterial phosphatidylethanolamine in decane. This ion movement was essentially confined to the membrane in terior during the current transients. Charge movement through the interior of the membrane during the current transients was studied as a function of the applied potential. The transferred charge approached an upper limit with increasing potential, which is interpreted to be the amount of charge due to tetraphenylborate ions absorbed into the boundary regions of the bilayer. A further analysis of the charge transfer as a function of potential indicates that the movement of tetraphenylborate ions is only influenced by a certain farction of the applied potential. For bacterial phosphatidylethanolamine bilayers the effective potential is 77 +/- 4% of the applied potential. The initial conductance and the time constant of the current transients were studied as a function of the applied potential using a Nernst-Planck electrodiffusion regime. It was found that an image-force potential energy barrier gave a good prediction of the observed behavior, provided that the effective potential was used in the calculations. We could not get a satisfactory prediction of the observed behavior with an Eyring rate theory model or a trapezoidal potential energy barrier.     

Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

Transmembrane electrostatic membrane potential is a major energy source of the cell. Importantly, it determines the structure as well as function of charge‐carrying membrane proteins. Here, we discuss the relationship between membrane potential and membrane proteins, in particular whether the conformation of these proteins is integrally connected to the membrane potential. Together, these concepts provide a framework for rationalizing the types of conformational changes that have been observed in membrane proteins and for better understanding the electrostatic effects of the membrane potential on both reversible as well as unidirectional dynamic processes of membrane proteins.     

Determination of zeta potential in Planctomycetes and its application in heavy metals toxicity assessment

Zeta potential of Planctomycetes was evaluated under different environmental conditions and correlated to cell viability. Phylogenetically distinct strains of the Planctomycetes presented different negative zeta potential values. More negative values were associated with Rhodopirellula spp. and related to the great amount of fimbriae in these species. Milli-Q water was chosen as the best dispersion media to perform the measurements. Zeta potential increased with ionic strength and varied with pH. In the physiological range of pH 5.0-9, zeta potential remained low and Rhodopirellula sp. strain LF2 cells were viable. Out of this range, zeta potential increased significantly and viability decreased. The effect on zeta potential of arsenic, cadmium, chromium, copper, lead, nickel, and zinc was assessed in Rhodopirellula sp. strain LF2. Zeta potential increased with increasing toxicity of the heavy metals in a dose-response way. This result was confirmed by the results observed for Rhodopirellula baltica strain SH1 under copper toxicity. Lead was the most toxic metal and zinc was the least toxic as observed by zeta potential and viability. The results support a correlation between zeta potential and cell viability which seem to indicate the possibility to use it as a viability predictor for the effects of heavy metals toxicity.     

Electrical response of beef-heart submitochondrial particles bound to phospholipid-impregnated millipore filters during ATP hydrolysis

1. Beef heart submitochondrial particles bound to asolectin impregnated Millipore filter, according to the method described earlier (Drachev et al. (1974) Nature 249, 321--324), are able to generate, upon addition of ATP, an electrical potential which can be directly measured. 2. The transmembrane electrical potential generated by ATP hydrolysis reaches values up to 80 mV. The half-time required to attain the plateau of potential is paradoxically long (5 to 10 min at room temperature) and is temperature-dependent. Among different phospholipid species which have been used to impregnate the Millipore filter, phosphatidylethanolamine was found to be the most effective for generation of electrical potential. 3. The potential generated by ATP hydrolysis is inhibited by inhibitors of mitochondrial ATPase, by the uncoupler FCCP and by reagents collapsing the membrane potential. 4. Addition of inhibitors of mitochondrial ATPase, when the plateau of potential is attained, results in a decay of potential. This decay of potential is as slow as the generation of potential induced by ATP hydrolysis. 5. The initial rise in electrical potential is proportional to the ATPase activity.     

Carnosine: from exercise performance to health

Carnosine was first discovered in skeletal muscle, where its concentration is higher than in any other tissue. This, along with an understanding of its role as an intracellular pH buffer has made it a dipeptide of interest for the athletic population with its potential to increase high-intensity exercise performance and capacity. The ability to increase muscle carnosine levels via β-alanine supplementation has spawned a new area of research into its use as an ergogenic aid. The current evidence base relating to the use of β-alanine as an ergogenic aid is reviewed here, alongside our current thoughts on the potential mechanism(s) to support any effect. There is also some emerging evidence for a potential therapeutic role for carnosine, with this potential being, at least theoretically, shown in ageing, neurological diseases, diabetes and cancer. The currently available evidence to support this potential therapeutic role is also reviewed here, as are the potential limitations of its use for these purposes, which mainly focusses on issues surrounding carnosine bioavailability.     

Bioelectric behaviour of intestinal wall in the earthworm Scherotheca sp (author's transl)]

Transmural potential difference (TPD) and short circuit current in the Scherotheca sp. intestinal wall in in vitro preparations have been studied, as well as their variations as related to ionic substitutions. Sodium ion seems to participate the most in the genesis of registered potential, so that its total substitution in the medium brings about the disappearance of the potential. Transmural potential relies on metabolic energy and is inhibited by N2, 2,4-DNP and CNK. Ouabain inhibits TPD only when present on the serosal side. This might indicate the existence on that side of a Na+ pump responsible for the active transport of the cation from mucosal.     

Influence of rotational energy barriers to the conformational search of protein loops in molecular dynamics and ranking the conformations.

An adjustable-barrier dihedral angle potential was added as an extension to a novel, previously presented soft-core potential to study its contribution to the efficacy of the search of the conformational space in molecular dynamics. As opposed to the conventional soft-core potential functions, the leading principle in the design of the new soft-core potential, as well as of its extension, the soft-core and adjustable-barrier dihedral angle (SCADA) potential (referred as the SCADA potential), was to maintain the main equilibrium properties of the original force field. This qualifies the methods for a variety of a priori modeling problems without need for additional restraints typically required with the conventional soft-core potentials. In the present study, the different potential energy functions are applied to the problem of predicting loop conformations in proteins. Comparison of the performance of the soft-core and SCADA potential showed that the main hurdles for the efficient sampling of the conformational space of (loops in) proteins are related to the high-energy barriers caused by the Lennard-Jones and Coulombic energy terms, and not to the rotational barriers, although the conformational search can be further enhanced by lowering the rotational barriers of the dihedral angles. Finally, different evaluation methods were studied and a few promising criteria found to distinguish the near-native loop conformations from the wrong ones.     

Temperature and growth-induced water potential

When the steins of dark-grown soybean [Glycine max (L.) Merr.] seedlings grew rapidly at favorable temperatures in saturating humidities, a water potential of about 0·2 MPa was induced by growth ($pS_o-$pS_w, where $pS_o is the water potential of the basal nonelongating tissue and $pS_w is the water potential of the elongating tissue). If this water potential was caused by high concentrations of solute in the apoplast, as has been proposed, lowering the temperature should have little effect on the potential. On the other hand, if the water potential was caused by apoplast tensions generated by growth, then the tensions should disappear as growth is inhibited by low temperatures. We observed that the growth-induced water potential became too small to detect when growth was inhibited by temperatures as low as 13—5 °C. The disappearance was observed as a rise in apoplast water potential using a thermocouple psychrometer for intact plants, a rise in cell turgor using a miniature pressure probe and a decrease in apoplast tensions using a pressure chamber. The disappearance was not caused by a loss of solute from the apoplast because the tensions fully accounted for the growth-induced water potential at all temperatures. The results are consistent with the lack of solute measured directly in the apoplast solutions at high temperatures (Nonami & Boyer 1987). Therefore, it was concluded that little solute was present in the apoplast at any temperature, and the growth-induced water potential was associated mostly with a tension that moved water from the xylem and into the surrounding cells to meet the demand of cell enlargement.     

Effect of high pH on the plasma membrane potential and conductance in Elodea densa

In leaves of Elodea densa the membrane potential measured in light equals the equilibrium potential of H+ on the morphological upper plasma membrane. The apoplastic pH on the upper side of the leaf is as high as 10.5-11.0, which indicates that alkaline pH induces an increased H+ permeability of the plasmalemma. To study this hypothesis in more detail we investigated the changes in membrane potential and conductance in response to alterations in the external pH from 7 (= control) to 9 or 11 under both light and dark conditions. Departing from the control pH 7 condition, in light and in dark the application of pH 9 resulted in a depolarization of the membrane potential to the Nernst potential of H+. In the light but not in the dark, this depolarization was followed by a repolarization to about -160 mV. The change to pH 9 induced, in light as well as in dark, an increase in membrane conductance. The application of pH 11, which caused a momentary hyper- or depolarization depending on the value at the time pH 11 was applied, brought the membrane potential to around -160 mV. The membrane conductance also increased, in comparison to its value at pH 7, as a result of the application of pH 11, irrespective of the light conditions.