2,272 research outputs found

    Asymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons.

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    In the Drosophila antenna, different subtypes of olfactory receptor neurons (ORNs) housed in the same sensory hair (sensillum) can inhibit each other non-synaptically. However, the mechanisms underlying this underexplored form of lateral inhibition remain unclear. Here we use recordings from pairs of sensilla impaled by the same tungsten electrode to demonstrate that direct electrical ("ephaptic") interactions mediate lateral inhibition between ORNs. Intriguingly, within individual sensilla, we find that ephaptic lateral inhibition is asymmetric such that one ORN exerts greater influence onto its neighbor. Serial block-face scanning electron microscopy of genetically identified ORNs and circuit modeling indicate that asymmetric lateral inhibition reflects a surprisingly simple mechanism: the physically larger ORN in a pair corresponds to the dominant neuron in ephaptic interactions. Thus, morphometric differences between compartmentalized ORNs account for highly specialized inhibitory interactions that govern information processing at the earliest stages of olfactory coding

    Outer Hair Cell Somatic Electromotility In Vivo and Power Transfer to the Organ of Corti

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    AbstractThe active amplification of sound-induced vibrations in the cochlea, known to be crucial for auditory sensitivity and frequency selectivity, is not well understood. The outer hair cell (OHC) somatic electromotility is a potential mechanism for such amplification. Its effectiveness in vivo is putatively limited by the electrical low-pass filtering of the cell's transmembrane potential. However, the transmembrane potential is an incomplete metric. We propose and estimate two metrics to evaluate the effectiveness of OHC electromotility in vivo. One metric is the OHC electromechanical ratio defined as the amplitude of the ratio of OHC displacement to the change in its transmembrane potential. The in vivo electromechanical ratio is derived from the recently measured in vivo displacements of the reticular lamina and the basilar membrane at the 19 kHz characteristic place in guinea pigs and using a model. The ratio, after accounting for the differences in OHC vibration in situ due to the impedances from the adjacent structures, is in agreement with the literature values of the in vitro electromechanical ratio measured by others. The second and more insightful metric is the OHC somatic power. Our analysis demonstrates that the organ of Corti is nearly optimized to receive maximum somatic power in vivo and that the estimated somatic power could account for the active amplification

    Formation of Intracardiac Electrograms under Physiological and Pathological Conditions

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    This work presents methods to advance electrophysiological simulations of intracardiac electrograms (IEGM). An experimental setup is introduced, which combines electrical measurements of extracellular potentials with a method for optical acquisition of the transmembrane voltage in-vitro. Thereby, intracardiac electrograms can be recorded under defined conditions. Using experimental and clinical signals, detailed simulations of IEGMs are parametrized, which can support clinical diagnosis

    A Biophysical Model of the Role of the Outer Hair Cell in Cochlear Nonlinearity

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    It has been observed that the response characteristics of the basilar membrane in normal living cochleae are both frequency and level-sensitive (Robles & Ruggero 2001). The quality factor of the tuning curve is large at low sound levels and decreases as the sound level increases, and the peak of the tuning curve moves towards lower frequencies as the sound level increases. The current study proposes a nonlinear cochlear model that responds adaptively to the incoming sounds via feedback control arising from the mechanical attributes of the cochlear partition. These attributes are dependent on the membrane potential of the outer hair cells (He & Dallos 1999, Santos-Sacchi 1992). A parallel resistor-capacitor circuit analogy of the outer hair cell with related perilymph and endolymph potentials is designed to simulate sound-evoked changes in the outer hair cell membrane potential. Nonlinear responses of the cochlea, such as compression and two tone suppression, can be explained using this model. Furthermore, it has been shown that the basilar membrane response to pure tone stimuli is attenuated by directly stimulating the medial olivo-cochlear bundle using electrical shocks (Cooper & Guinan 2006). Basilar membrane responses in the presence of efferent stimulation can be demonstrated using the same model, through modulation of the outer hair cell rnembrane potential. The proposed model provides a unified account of the combined effect of sounds and efferent stimulation on cochlear responses

    Molecular Dynamics Simulations to Probe Effects of Ultra-Short, Very-High Voltage Pulses on Cells

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    The use of very high electric fields (∼ 100kV/cm or higher) with pulse durations in the nanosecond range (Ultra-short) has been a very recent development in bioelectrics. Traditionally, the electric field effects have mostly been confined to: (a) low field, long-duration pulses, and (b) focused mainly on electroporation studies. Thus, aspects such as possible field-induced DNA damage, calcium release, alterations in neuro-transmitters, or voltage-gating have generally been overlooked. Ultra-short, high-field pulses open the way to targeted and deliberate apoptotic cell killing (e.g., of tumor cells). Though experimental data is very useful, it usually yields information on macroscopic variables that is inherently an average over time and/or space. Measurements often do not provide the molecular level information or details, as might be possible through numerical simulations. Also, the relevance and relative role of underlying physical mechanisms cannot be probed. With developments in computer technology, rapid advances in numerical algorithms for parallel computing, and with increasing computational resources, computer simulations of cellular dynamics and biological phenomena is gaining increasing popularity. A range of simulation methods exist that span the macroscopic continuum approaches (e.g. the Smoluchowski equation), to those based on the semi-classical retarded Langevin and Green\u27s functions, to microscopic-kinetic analyses based on Brownian dynamics or Molecular Dynamics (MD). Here we focus on the MD technique, as it provides the most comprehensive, time-dependent, three-dimensional nanoscale analyses with inclusion of the many-body aspects. This dissertation research presents simulations and analyses of lipid membrane poration and its dynamics, predictions of transport parameters under high-field, non-equilibrium conditions, electric fields effects on DNA, micelle disintegration, protein unfolding and intra-cellular calcium release. The following results have been found as a result of the application of external electric fields on cells: (a) Poration due to the re-orientation of the lipid molecules within the lipid bilayer, (b) Externalization of charged molecules such as Phosphotidyl Serine (PS), (c) Dramatic lowering of permittivity and diffusion coefficient with spatially structured layering of the membrane nanopore, (d) DNA alignment in the direction of electric field and eventual fragmentation, (e) Calcium release from the endoplasmic reticulum (ER) leading to time-dependent oscillatory waves and (f) Membrane fragmentation upon the application of high external fields

    Analytical Modeling of a Communication Channel Based on Subthreshold Stimulation of Neurobiological Networks

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    The emergence of wearable and implantable machines manufactured artificially or synthesized biologically opens up a new horizon for patient-centered health services such as medical treatment, health monitoring, and rehabilitation with minimized costs and maximized popularity when provided remotely via the Internet. In particular, a swarm of machines at the scale of a single cell down to the nanoscale can be deployed in the body by the non-invasive or minimally invasive operation (e.g., swallowing and injection respectively) to perform various tasks. However, an individual machine is only able to perform basic tasks so it needs to exchange data with the others and outside world through an efficient and reliable communication infrastructure to coordinate and aggregate their functionalities. We introduce in this thesis Neuronal Communication (NC) as a novel paradigm for utilizing the nervous system \emph{in vivo} as a communication medium to transmit artificial data across the body. NC features body-wide communication coverage while it demands zero investment cost on the infrastructure, does not rely on any external energy source, and exposes the body to zero electromagnetic radiation. n addition, unlike many conventional body area networking techniques, NC is able to provide communication among manufactured electronic machines and biologically engineered ones at the same time. We provide a detailed discussion of the theoretical and practical aspects of designing and implementing distinct paradigms of NC. We also discuss NC future perspectives and open challenges. Adviser: Massimiliano Pierobo

    The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

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    Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

    Structural dynamics of the selectivity filter in HCN1 ion channel

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    Les canaux HCN (cycliques nucléotidiques) activés par hyperpolarisation appartiennent à la superfamille des canaux cationiques voltage-dépendants et sont responsables de la génération de courant drôle (If) dans les cellules cardiaques et neuronales. Malgré la similitude structurelle globale avec le potassium voltage-dépendant (Kv) et les canaux ioniques cycliques nucléotidiques (CNG), ils montrent un modèle de sélectivité distinctif pour les ions K+ et Na+. Plus précisément, leur perméabilité accrue aux ions Na+ est essentielle à son rôle dans la dépolarisation des membranes cellulaires. Ils sont également l'une des seules protéines connues à sélectionner entre les ions Na+ et Li+, faisant des HCN des canaux semi-sélectifs. Ici, nous étudions les propriétés de sélectivité uniques des canaux HCN à l'aide de simulations de dynamique moléculaire. Nos simulations suggèrent que le pore HCN1 est très flexible et dilaté par rapport aux canaux Kv et qu'il n'y a qu'un seul site de liaison ionique stable dans le filtre de sélectivité qui les distingue des canaux Kv et CNG. Nous observons également que la coordination et l'hydratation des ions diffèrent dans le filtre de sélectivité de HCN1 par rapport aux canaux Kv et CNG. De plus, la coordination des ions K+ par les groupes carbonyle du filtre de sélectivité est plus stable par rapport aux ions Na+ et Li+, ce qui peut expliquer les propriétés de sélectivité distinctes du canal.Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the voltage-gated cation channel superfamily and are responsible for the generation of funny current (If) in cardiac and neuronal cells. Despite the overall structural similarity to voltage-gated potassium (Kv) and cyclic nucleotide-gated (CNG) ion channels, they show distinctive selectivity pattern for K+ and Na+ ions. Specifically, their increased permeability to Na+ ions is critical to its role in depolarizing cellular membranes. They are also one of the only known proteins to select between Na+ and Li+ ions, making HCNs semi-selective channels. Here we investigate the unique selectivity properties of HCN channels using molecular dynamics simulations. Our simulations suggest that the HCN1 pore is very flexible and dilatated compared to Kv channels and that there is only one stable ion binding site within the selectivity filter which discriminates them from both Kv and CNG channels. We also observe that ion co-ordination and hydration differ within the selectivity filter of HCN1 compared to Kv and CNG channels. Additionally, the co-ordination of K+ ions by the carbonyl groups of the selectivity filter is more stable compared to Na+ and Li+ ions, which may explain the channel's distinct selectivity properties
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