Voltage-gated sodium channels in taste bud cells

Background  

Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown.     

Absolute spectroscopic determination of cross-membrane potential

Spectroscopic determination of the cross-membrane electric potential has been used for more than 20 years. This method, which usually employs absorption or fluorescence measurements, allows for a rapid and noninvasive study of the electrical properties of the membranes of cells and liposomes. However, the usual fluorescence techniques preferably allow monitoring changes in the potential on triggerable or excitable membranes, and not the absolute value of the potential. They also do not provide means for measuring the potential on single cells. This paper reviews three methods that solve these issues. Nernstian dyes which partition between intra-and extracompartmental volumes enable a fluorescence microscopic determination of a single cell and even a single organelle. Dual-wavelength ratiometric recording from membrane-staining dyes also provides means for measuring the field on a single cell. Resonance Raman probes provide a spectroscopic method with a natural internal standard for the absolute measurement of membrane potential.     

A primary mechanism for spiral wave meandering

The stability and dynamics of spiral wave meandering were studied by examining the behavior of small perturbations to a steadily rotating action potential wave. The disturbances responsible for meandering were found to be generated through an interaction between the unstable local linear dynamics characteristic of the action potential trailing edge near the core and perturbations existing in the region immediately behind this edge. Significantly, for the cases studied, neither wavefront curvature nor head-tail interactions were involved in this process. Study of the generation mechanism using a series of representative mathematical models and computer experiments led to the prediction that the following features of rotating action potentials render them more susceptible to meandering: (1) proximity of the wave tip to the center of rotation, (2) wider action potential leading and trailing edges, and (3) slower wave rotation speeds. Variation of basic tissue properties, including firing threshold potentials and excitability above threshold, affected these properties, and those of the perturbation dynamics, in several ways, producing both stabilizing and destabilizing effects. The nature of the involvement of various tissue and membrane electrical properties is therefore complex, affecting several factors relevant to meandering at once. (c) 2002 American Institute of Physics.     

A virtual instrumentation based protocol for the automated implementation of the inner field compensation method

One influential parameter which mediates interactions between many types of molecules and biological membranes stems from the lumped contributions of the transmembrane potential, dipole potential and the difference in the surface potentials on both sides of a membrane. With relevance to cell physiology, such electrical features of a biomembrane are prone to undergoing changes as a result of interactions with the aqueous surrounding. Among the most useful tools devoted to exploring changes of electrical parameters of a lipid membrane induced by certain extracellular ions, lipid composition, and embedded membrane peptides and proteins, are spectroscopic imaging and the inner field compensation (IFC) method. In this work we layout the principles of a fully computerized version of the IFC method, which makes it more readily available to users. As a direct application, we deployed this improved version of the IFC method to time-resolve changes induced by alamethicin monomers upon membrane dipole potential, following their aggregation within an artificial lipid membrane. Intriguingly, even prior crossing the membrane core, the membrane-bound alamethicin monomers are shown to significantly increase the dipole potential of the monolayer they reside in. Such data further emphasize the yet less-explored interplay between membrane-based protein and peptides, and the membrane dipole potential.     

A biophysical model of an inner hair cell

Whole-cell patch-clamp recordings on isolated inner hair cells (IHCs) of guinea pig cochleae have revealed the presence of voltage-gated potassium channels. A biophysical model of an IHC is presented that indicates activation of slow voltage-gated potassium channels may lead to receptor potentials whose dc component decreases during the stimulus, and membrane potential hyperpolarizes when the stimulus is turned off. Both the decreasing dc and the hyperpolarization are, respectively, consistent with rapid adaptation and suppression of spontaneous rate in the auditory nerve. Receptor potentials recorded in vivo do not show these features, and when a nonspecific leak is included in the model to simulate microelectrode impalement, the model's receptor potentials become similar to those in vivo. The nonspecific leak creates an electrical shunt that masks slow channel activity and allows the cell to depolarize. Both the decreasing dc and the hyperpolarization are sensitive to the resting potential. Because the reported resting potentials in vivo and in vitro differ greatly, the model is used to investigate homeostatic mechanisms responsible for the resting potential. It is found that the voltage-gated potassium channels have the greatest influence on the resting potential, but that the standing transducer current may be sufficient to eliminate the decreasing dc and after-stimulus hyperpolarization.     

Model of the appearance of avalanche bioelectric discharges in neural networks of the brain

According to neurobiological experiments, the effect of the appearance of spontaneous bioelectric discharges in neural networks of the brain satisfies the statistics of self-organized criticality. Theoretical investigations indicate that the critical behavior is an optimal regime for the storage and processing of information in the brain. Many model works focused on the approximation of the experimental data and on the investigation of information characteristics of signals, whereas the problem of dynamical mechanisms of their avalanche generation remains almost unstudied. The conditions of the appearance of high-frequency discharges at the critical dynamical threshold have been analyzed in the framework of the biophysical model of the neuronal network. A probabilistic model of the layer-by-layer activation of cells, which makes it possible to estimate the key relations between the parameters for avalanche generation of the discharge, has been proposed.     

Macroscopic models of internal dynamics of electrical discharges

The existence of thresholds for electrical discharge onset suggests a functional relation between macroscopic resistivity and current. At low current, the resistivity should be inversely proportional to the magnitude of the current. Macroscopic models which employ this scaling predict many empirically observed properties of transient electrical discharges such as: (i) thresholds for the onset of current, (ii) the abrupt termination of current in active regions of a current channel, (iii) current restart in passive regions of current channels, (iv) leaders, and (v) residual charge, both in channels and at sources when current terminates. An overview of research with these models is presented and examples are used to illustrate the results that have been obtained. These models are shown to predict current channel formation and describe results of efforts to benchmark theory with experimental data     

Temporal resolution and temporal integration of short pulses at the auditory periphery of echolocating animals

To explain the temporal integration and temporal resolution abilities revealed in echolocating animals by behavioral and electrophysiological experiments, the peripheral coding of sounds in the high-frequency auditory system of these animals is modeled. The stimuli are paired pulses similar to the echolocating signals of the animals. Their duration is comparable with or smaller than the time constants of the following processes: formation of the firing rate of the basilar membrane, formation of the receptor potentials of internal hair cells, and recovery of the excitability of spiral ganglion neurons. The models of auditory nerve fibers differ in spontaneous firing rate, response thresholds, and abilities to reproduce small variations of the stimulus level. The formation of the response to the second pulse of a pair of pulses in the multitude of synchronously excited high-frequency auditory nerve fibers may occur in only two ways. The first way defined as the stochastic mechanism implies the formation of the response to the second pulse as a result of the responses of the fibers that did not respond to the first pulse. This mechanism is based on the stochastic nature of the responses of auditory nerve fibers associated with the spontaneous firing rate. The second way, defined as the repeatition mechanism, implies the appearance of repeated responses in fibers that already responded to the first pulse but suffered a decrease in their response threshold after the first spike generation. This mechanism is based on the deterministic nature of the responses of fibers associated with refractoriness. The temporal resolution of pairs of short pulses, which, according to the data of behavioral experiments, is about 0.1–0.2 ms, is explained by the formation of the response to the second pulse through the stochastic mechanism. A complete recovery of the response to the second pulse, which, according to the data of electrophysiological studies of short-latency evoked brainstem potentials in dolphins, occurs within 5 ms, is explained by the formation of the response to the second pulse through the repetition mechanism. The time constant of temporal integration, which, according to the behavioral experiments at threshold levels of pulses, is about 0.2–0.3 ms, is explained by the integrating properties of internal hair cells, etc. It is shown that, at the high-frequency auditory periphery, the temporal integration imposes no limitations on the temporal resolution, because both integration and resolution are different characteristics of the same multiple response of synchronously excited fibers.     

数字信号在原子芯片中的应用

通过分析和计算不同谐波分量与原子相互作用产生不同的势场,发现可以将其叠加在一起形成原子囚禁势,提出了数字信号在原子芯片中的应用方案. 关键词： 原子芯片 数字信号 绝热势     

Coupling of Simultaneous Fluorescence and Electrophysiology: Historical Survey, Contributions, and Prospects

The coupling of simultaneous fluorescence and eleclrophysiological measurements paved the way for the development of potentiometric and intracellular free ion-sensitive probes, although the basic and initial aim of these combined studies remains to record fast conformational changes during ion channel activation. Recent high-resolution studies of some channels put back on the agenda challenging methods that combine spectroscopy and electrophysiology. Fluorescence is certainly the most versatile and sensitive spectroscopy in this kind of experiment, and we have recently witnessed significant breakthroughs, at the level of whole cells with intact or mutated channels or with planar lipid bilayers doped with channels or their peptide models. After our initial study of membrane dynamics associated with excitability, following transient pyrene excimer signals during action potentials or voltage-clamp of nerve fibers, we tested the feasability of FRAP (fluorescence recovery after photobleaching) experiments on planar lipid bilayers. This technique was later applied to lateral diffusion measurements of channel forming peptides (alamethicin labeled with fluorescein and the voltage-sensitive segment S4 of the Shaker potassium channel labeled with NBD) under applied voltage. We provide independent evidence for voltage-dependent partitioning and transmembrane insertion and propose renewed experimental avenues to reveal movements and conformational changes associated with ion channel gating and opening.     

Spatio-temporal invariants of the time reversal operator

The decomposition of the time reversal operator, known by the French acronym DORT, is a technique to extract point scatterers' monochromatic Green's functions from a medium. It is used to detect, locate, and focus on scatterers in various domains such as underwater acoustics, medical ultrasound, and nondestructive evaluation. A limitation of the method arises from its single-frequency nature, when the signals used in acoustics are often broadband. Reconstruction of the broadband Green's functions from the single-frequency Green's functions can be very difficult when numerous scatterers are present in the medium. Moreover, the method does not take advantage of the axial resolution associated with broadband signals. Time domain methods are investigated here as an answer to these problems. It is shown that the time reversal operator in the time domain takes the form of a tensor. The properties of the invariants are discussed. It is shown they do not have all the expected properties. Another method is proposed that requires a priori information on the medium.     

Spontaneous onset of atrial fibrillation

Most commonly, atrial fibrillation is triggered by rapid bursts of electrical impulses originating in the myocardial sleeves of pulmonary veins (PVs). However, the nature of such bursts remains poorly understood. Here, we propose a mechanism of bursting consistent with the extensive empirical information about the electrophysiology of the PVs. The mechanism is essentially non-local and involves the spontaneous initiation of non-sustained spiral waves in the distal end of the muscle sleeves of the PVs. It reproduces the experimentally observed dynamics of the bursts, including their frequency, their intermittent character, and the unusual shape of the electrical signals in the pulmonary veins that are reminiscent of so-called early afterdepolarizations (EADs).     

Simulation of mass transfer in systems with isotropic pair correlation of particles

Results of a numerical analysis of mass transfer in systems of macroscopic particles with various isotropic interaction potentials are presented. Parameters that determine transport properties of nonideal dissipative systems are obtained for a broad class of model potentials. An approximate expression for the diffusivity of interacting particles is proposed. The relationship between diffusivity and viscosity is analyzed for strongly nonideal systems.     

Heat generation properties determined by chemical potentials

We investigate the current-induced heat generation in a quantum dot (QD) coupled to four spin chemical potentials, which originate from the magnetic pumping field applied on the QD. Both resonant and non-resonant electron tunneling process is analyzed. It is found that the heat generation characteristic is mainly determined by the two spin chemical potentials lying nearest to the dot level. In particular, when the difference of this two potentials is less than two phonon energy, the heat generation exhibits quantum properties, unique behavior to nanosystems and absent in macroscopic bulks.     

Multiscale simulation of loading and electrical resistance in silicon nanoindentation

Nanoindentation experiments are an excellent probe of micromechanical properties, but their interpretation is complicated by their multiscale nature. We report simulations of silicon nanoindentation, based on an extended version of the local quasicontinuum model, capable of handling complex Bravais crystals. Our simulations reproduce the experimental load vs displacement curves and provide microscopic information such as the distribution of transformed metallic phases of silicon underneath the indenter. This information is linked to the macroscopic electrical resistance, giving a satisfactory explanation of experimental results.     

Information-theoretic measures for Morse and Pöschl–Teller potentials

The spreading of the quantum-mechanical probability cloud for the ground state of the Morse and modified Pöschl–Teller potentials, which controls the chemical and physical properties of some molecular systems, is studied in position and momentum space by means of global (Shannon's information entropy, variance) and local (Fisher's information) information-theoretic measures. We establish a general relation between variance and Fisher's information, proving that, in the case of a real-valued and symmetric wavefunction, the well-known Cramer–Rao and Heisenberg uncertainty inequalities are equivalent. Finally, we discuss the asymptotics of all three information measures, showing that the ground state of these potentials saturates all the uncertainty relations in an appropriate limit of the parameter.     

On the use of information theory for the analysis of the relationship between neural and imaging signals

Functional magnetic resonance imaging (fMRI) is a widely used method for studying the neural basis of cognition and of sensory function. A potential problem in the interpretation of fMRI data is that fMRI measures neural activity only indirectly, as a local change of deoxyhemoglobin concentration due to the metabolic demands of neural function. To build correct sensory and cognitive maps in the human brain, it is thus crucial to understand whether fMRI and neural activity convey the same type of information about external correlates. While a substantial experimental effort has been devoted to the simultaneous recordings of hemodynamic and neural signals, so far, the development of analysis methods that elucidate how neural and hemodynamic signals represent sensory information has received less attention. In this article, we critically review why the analytical framework of information theory, the mathematical theory of communication, is ideally suited to this purpose. We review the principles of information theory and explain how they could be applied to the analysis of fMRI and neural signals. We show that a critical advantage of information theory over more traditional analysis paradigms commonly used in the fMRI literature is that it can elucidate, within a single framework, whether an empirically observed correlation between neural and fMRI signals reflects either a similar stimulus tuning or a common source of variability unrelated to the external stimuli. In addition, information theory determines the extent to which these shared sources of stimulus signal and of variability lead fMRI and neural signals to convey similar information about external correlates. We then illustrate the formalism by applying it to the analysis of the information carried by different bands of the local field potential. We conclude by discussing the current methodological challenges that need to be addressed to make the information-theoretic approach more robustly applicable to the simultaneous recordings of neural and imaging data.     

Testing methodologies for the nonlinear analysis of causal relationships in neurovascular coupling

We investigated the use and implementation of a nonlinear methodology for establishing which changes in neurophysiological signals cause changes in the blood oxygenation level-dependent (BOLD) contrast measured in functional magnetic resonance imaging. Unlike previous analytical approaches, which used linear correlation to establish covariations between neural activity and BOLD, we propose a directed information-theoretic measure, the transfer entropy, which can elucidate even highly nonlinear causal relationships between neural activity and BOLD signal. In this study we investigated the practicality of such an analysis given the limited data samples that can be collected experimentally due to the low temporal resolution of BOLD signals. We implemented several algorithms for the estimation of transfer entropy and we tested their effectiveness using simulated local field potentials (LFPs) and BOLD data constructed to match the main statistical properties of real LFP and BOLD signals measured simultaneously in monkey primary visual cortex. We found that using the advanced methods of entropy estimation implemented and described here, a transfer entropy analysis of neurovascular coupling based on experimentally attainable data sets is feasible.