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PubMed2004

Contributions of advective and diffusive oxygen transport through multilayer composite caps over mine waste.

The relative contributions of four mechanisms of oxygen transport in multilayer composite (MLC) caps placed over oxygen-consuming mine waste were evaluated using numerical and analytical methods. MLC caps are defined here as caps consisting of earthen and geosynthetic (polymeric) components where a composite barrier layer consisting of a geomembrane (1-2 mm thick polymeric sheet) overlying a clay layer is the primary barrier to transport. The transport mechanisms that were considered are gas-phase advective transport, gas-phase diffusive transport, liquid-phase advective transport via infiltrating precipitation and liquid-phase diffusive transport. A numerical model was developed to simulate gas-phase advective-diffusive transport of oxygen through a multilayer cap containing seven layers. This model was also used to simulate oxygen diffusion in the liquid phase. An approximate analytical method was used to compute the advective flux of oxygen in the liquid phase. The numerical model was verified for limiting cases using an analytical solution. Comparisons were also made between model predictions and field data for earthen caps reported by others. Results of the analysis show that the dominant mechanism for oxygen transport through MLC caps is gas-phase diffusion. For the cases that were considered, the gas-phase diffusive flux typically comprises at least 99% of the total oxygen flux. Thus, designers of MLC caps should focus on design elements and features that will limit diffusion of gas-phase oxygen.

Chemical Precipitation↗

PubMed2004

Correction of spin diffusion during iterative automated NOE assignment.

Indirect magnetization transfer increases the observed nuclear Overhauser enhancement (NOE) between two protons in many cases, leading to an underestimation of target distances. Wider distance bounds are necessary to account for this error. However, this leads to a loss of information and may reduce the quality of the structures generated from the inter-proton distances. Although several methods for spin diffusion correction have been published, they are often not employed to derive distance restraints. This prompted us to write a user-friendly and CPU-efficient method to correct for spin diffusion that is fully integrated in our program ambiguous restraints for iterative assignment (ARIA). ARIA thus allows automated iterative NOE assignment and structure calculation with spin diffusion corrected distances. The method relies on numerical integration of the coupled differential equations which govern relaxation by matrix squaring and sparse matrix techniques. We derive a correction factor for the distance restraints from calculated NOE volumes and inter-proton distances. To evaluate the impact of our spin diffusion correction, we tested the new calibration process extensively with data from the Pleckstrin homology (PH) domain of Mus musculus beta-spectrin. By comparing structures refined with and without spin diffusion correction, we show that spin diffusion corrected distance restraints give rise to structures of higher quality (notably fewer NOE violations and a more regular Ramachandran map). Furthermore, spin diffusion correction permits the use of tighter error bounds which improves the distinction between signal and noise in an automated NOE assignment scheme.

Algorithms↗

PubMed2006

How accurately can the parameters from a model of anisotropic 3He gas diffusion in lung acinar airways be estimated? Bayesian view.

In the framework of a recently proposed method for in vivo lung morphometry, acinar lung airways are considered as a set of randomly oriented cylinders covered by alveolar sleeves. Diffusion of (3)He in each airway is anisotropic and can be described by distinct longitudinal and transverse diffusion coefficients. This macroscopically isotropic but microscopically anisotropic model allows estimation of these diffusion coefficients from multi b-value MR experiments despite the airways being too small to be resolved by direct imaging. Herein a Bayesian approach is used for analyzing the uncertainties in the model parameter estimates. The approach allows evaluation of relative errors of the parameter estimates as functions of the "true" values of the parameters, the signal-to-noise ratio, the maximum b-value and the total number of b-values used in the experiment. For a given set of the "true" diffusion parameters, the uncertainty in the estimated diffusion coefficients has a minimum as a function of maximum b-value and total number of data points. Choosing the MR pulse sequence parameters corresponding to this minimum optimizes the diffusion MR experiment and gives the best possible estimates of the diffusion coefficients. The mathematical approach presented can be generalized for models containing arbitrary numbers of estimated parameters.

Anisotropy↗

PubMed2004

Single-shot fast spin-echo diffusion tensor imaging of the brain and spine with head and phased array coils at 1.5 T and 3.0 T.

In this study, we investigated the use of a single-shot fast spin-echo-based sequence to perform diffusion tensor imaging (DTI) with improved anatomic fidelity through the entire brain and the cervical spine. Traditionally, diffusion tensor images have been acquired by single-shot echo-planar imaging (EPI) methods in which large distortions result from magnetic susceptibility effects, especially near air-tissue interfaces. These distortions can be problematic, especially in anterior and inferior portions of the brain, and they also can severely limit applications in the spine. At higher magnetic fields these magnetic susceptibility artifacts are increased. The single-shot fast spin-echo (SSFSE) method used in this study utilizes radiofrequency rephasing in the transverse plane and thus provides diffusion images with negligible distortion even at 3 Tesla. In addition, the SSFSE sequence does not require multiple fast-receivers, which are not available on many magnetic resonance (MR) systems. Phased array coils were used to increase the signal-to-noise ratio of the images, offering a major inherent advantage in diffusion tensor imaging of the spine and brain. The mean diffusion measurements obtained with the SSFSE acquisition were not statistically different (p > 0.05) from EPI-based acquisitions. Compared to routine T(2)-weighted MR images, the DTI-EPI sequence showed up to 20% in elongation of the brain in the anterior-posterior direction on a sagittal image due to magnetic susceptibility distortions, whereas in the DTI-SSFSE, the image distortions were negligible. The diffusion tensor SSFSE method was also able to assess diffusion abnormalities in a brain stem hemorrhage, unaffected by the spatial distortions that limited conventional EPI acquisition.

Adult↗

PubMed2005

Concentration-dependent self-diffusion of adsorbates in mesoporous materials.

The pulsed-field gradient NMR method has been applied to study self-diffusion of liquids in mesoporous materials with different pore sizes and morphologies as a function of pore loading. It is found that the effective diffusivities of adsorbate molecules in mesopores at partial loadings are related to two mechanisms, the Knudsen diffusion through the gaseous phase in the pore space and the diffusion within the layer of molecules adsorbed on the pore walls. The relative contributions of these modes, which are determined by the details of the interphase equilibrium, change with variation of the pore loading, leading to a complex behavior of the effective self-diffusion coefficient. The impact of the pore size and the adsorbate-surface interaction on self-diffusion is elucidated. Possible reasons for an experimentally obtained hysteresis in the diffusivities measured on adsorption and desorption in mesopores are discussed.

Adsorption↗

PubMed2005

White matter changes in multiple sclerosis: correlation of q-space diffusion MRI and 1H MRS.

OBJECTIVE: To explore the diagnostic usefulness of high b-value diffusion magnetic resonance brain imaging ("q-space" imaging) in multiple sclerosis (MS). More specifically, we aimed at evaluating the ability of this methodology to identify tissue damage in the so-called normal-appearing white matter (NAWM). DESIGN: In this study we examined the correlation between q-space diffusion imaging and magnetic resonance spectroscopy (MRS)-based two-dimensional 1H chemical shift imaging. Eight MS patients with different degree of disease severity and seven healthy subjects were scanned in a 1.5-T magnetic resonance imaging (MRI) scanner. The MRI protocol included diffusion tensor imaging (DTI) (with bmax of 1000 s/mm2), high b-value diffusion-weighted imaging (with bmax of 14,000 s/mm2) and 2D chemical shift imaging. The high b-value data set was analyzed using the q-space methodology to produce apparent displacement and probability maps. RESULTS: We found that the q-space diffusion displacement and probability image intensities correlated well with N-acetylaspartate levels (r=.61 and .54, respectively). Furthermore, NAWM that was abnormal on MRS was also found to be abnormal using q-space diffusion imaging. In these areas, the q-space displacement values increased from 3.8+/-0.2 to 4.6+/-0.6 microm (P<.02), the q-space probability values decreased from 7.4+/-0.3 to 6.8+/-0.3 (P<.002), while DTI revealed only a small, but still significant, reduction in fractional anisotropy values from 0.40+/-0.02 to 0.37+/-0.02 (P<.05). CONCLUSION: High b-value diffusion imaging can detect tissue damage in the NAWM of MS patients. Despite the theoretical limitation of this method, in practice it provides additional information which is clinically relevant for detection of tissue damage not seen in conventional imaging techniques.

Adult↗

PubMed2004

Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution.

Diffusion-weighted magnetic resonance imaging can provide information related to the arrangement of white matter fibers. The diffusion tensor is the model most commonly used to derive the orientation of the fibers within a voxel. However, this model has been shown to fail in regions containing several fiber populations with distinct orientations. A number of alternative models have been suggested, such as multiple tensor fitting, q-space, and Q-ball imaging. However, each of these has inherent limitations. In this study, we propose a novel method for estimating the fiber orientation distribution directly from high angular resolution diffusion-weighted MR data without the need for prior assumptions regarding the number of fiber populations present. We assume that all white matter fiber bundles in the brain share identical diffusion characteristics, thus implicitly assigning any differences in diffusion anisotropy to partial volume effects. The diffusion-weighted signal attenuation measured over the surface of a sphere can then be expressed as the convolution over the sphere of a response function (the diffusion-weighted attenuation profile for a typical fiber bundle) with the fiber orientation density function (ODF). The fiber ODF (the distribution of fiber orientations within the voxel) can therefore be obtained using spherical deconvolution. The properties of the technique are demonstrated using simulations and on data acquired from a volunteer using a standard 1.5-T clinical scanner. The technique can recover the fiber ODF in regions of multiple fiber crossing and holds promise for applications such as tractography.

Algorithms↗

PubMed2004

Mapping the orientation of intravoxel crossing fibers based on the phase information of diffusion circular spectrum.

A new method is presented to map the orientation of intravoxel crossing fibers by using the phase of the diffusion circular spectrum harmonics. In a previous study [Zhan, W., Gu, H., Xu, S., Silbersweig, D.A., Stern, E., Yang, Y., 2003. Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients. Magn. Reson. Med. 49, 1077-1088], we demonstrated that the magnitude of the 4th-order harmonic of the diffusion circular spectrum can be used to identify the existence of fiber crossings. However, the orientation of the intravoxel crossing fibers remained unknown. This study extends the diffusion circular spectrum mapping method so that it is able to identify the orientation of the intravoxel crossing fibers by utilizing the phase information of the circular spectrum. In general, the phase of the circular harmonic determines the rotation of the apparent diffusion coefficient (ADC) profile on the sampling circle that is spanned by the major and medium eigenvector of the diffusion tensor and thus can be used to determine the orientation of the crossing fibers. Simulation results show that the regular tensor-based major eigenvector maps have obvious artifacts in the fiber-crossing area, whereas the estimated crossing fibers by the proposed method are much more consistent with the orientation of the actual intravoxel fibers. Diffusion MRI experiments were performed on five healthy human brains using a 3T scanner. The brain regions with fiber crossings were selected by thresholding the magnitudes of the 4th-order circular spectrum map. Intravoxel crossing fibers were estimated by the phase of the 4th-order harmonic for each voxel within these areas. The estimated intravoxel crossing fibers demonstrated a clear consistency with the orientations of fiber tracks in the surrounding tissues, reducing the fiber orientation discontinuity of the regular major eigenvector map.

Adult↗

PubMed2005

Extracellular diffusivity determines contribution of high-versus low-affinity receptors to neural signaling.

Diffusion-weighted magnetic resonance imaging detects physiological changes in the human brain by highlighting alterations in local diffusivity. However, the causal link between brain tissue diffusivity and neural activity is poorly understood. Synaptic physiology studies in vitro coupled with biophysical modeling have suggested that extracellular diffusion affects the spatial profile of receptor activation during synaptic discharges. Here, we attempt to address this issue more directly, by recording synaptic currents from individual cells in acute brain slices while reducing the bath medium diffusivity by 25-30% (measured with two-photon microscopy) using inert dextran molecules. We find that retarding extracellular diffusion increases the activation of high-affinity NMDA, but not low-affinity AMPA, receptors in response to remote, spontaneous or evoked, synaptic releases of the common excitatory neurotransmitter glutamate. The results suggest that variations in extracellular diffusivity could reflect an altered contribution of higher- versus lower-affinity receptor types to the network activity of synaptic circuits.

Animals↗

PubMed2006

Collateral nerve fibers in human spinal cord: visualization with magnetic resonance diffusion tensor imaging.

Diffusion tensor magnetic resonance imaging provides structural information about nerve fiber tissue. The first eigenvector of the diffusion tensor is aligned with the nerve fibers, i.e., longitudinally in the spinal cord. The underlying hypothesis of this study is that the presence of collateral nerve fibers running orthogonal to the longitudinal fibers results in an orderly arrangement of the second eigenvectors. Magnetic resonance diffusion tensor scans were performed with line scan diffusion imaging on a clinical MR scanner. Axial sections were scanned in a human cervical spinal cord specimen at 625 microm resolution and the cervical spinal cord of four normal volunteers at 1250 microm resolution. The spinal cord specimen was fixed and stained for later light microscopy of the collateral fiber architecture at 0.53 microm resolution. Diffusion measured by MR was found to be anisotropic for both white and gray matter areas of the spinal cord specimen; the average fractional anisotropy (FA) was 0.63 +/- 0.09 (diffusion eigenvalues lambda1 0.38 +/- 0.05 micros/mm2, lambda2 0.14 +/- 0.03 micros/mm2, lambda3 0.10 +/- 0.03 micros/mm2) in white matter and 0.27 +/- 0.04 (lambda1 0.36 +/- 0.04 micros/mm2, lambda2 0.28 +/- 0.03 micros/mm2, lambda3 0.21 +/- 0.04 micros/mm2 in gray matter. The normal-volunteer FA values were similar, i.e., 0.66 +/- 0.04 (lambda1 1.66 +/- 0.14 micros/mm2, lambda2 0.55 +/- 0.02 micros/mm2, lambda3 0.40 +/- 0.01 micros/mm2) in white matter and 0.35 +/- 0.03 (lambda1 1.14 +/- 0.07 micros/mm2, lambda2 0.70 +/- 0.03 micros/mm2, lambda3 0.58 +/- 0.02 micros/mm2) in gray matter. The first eigenvector pointed, as expected, in the longitudinal direction. The second eigenvector directions exhibited a striking arrangement, consistent with the distribution of interconnecting collateral nerve fibers discerned on the histology section. This finding was confirmed for the specimen by quantitative pixel-wise comparison of second eigenvector directions and collateral fiber directions assessed on light microscopy image data. Diffusion tensor MRI can reveal non-invasively and in great detail the intricate fiber architecture of the human spinal cord.

Adult↗

PubMed2006

Quantitative analysis along the pyramidal tract by length-normalized parameterization based on diffusion tensor tractography: application to patients with relapsing neuromyelitis optica.

In this study, we introduced a length-normalized parameterization method to establish anatomical correspondence of white matter fiber tracts across subjects and applied this method to investigate the presence of abnormal diffusion along the pyramidal tract (PYT) of relapsing neuromyelitis optica (RNMO) patients without visible brain lesions. In this approach, the part of the PYT between the lowest slice of the cerebral peduncle and the uppermost slice of the lateral ventricle was reconstructed to establish the anatomical correspondence across subjects using diffusion tensor tractography. Then it was parameterized by normalizing its length and dividing equally the normalized length into a certain number of segments, so that the comparability of each segment across subjects along the PYT was established. Tract-specific diffusion indices, including directionally averaged diffusivity (D(av)), fractional anisotropy (FA), primary diffusivity (lambda(1)) and transverse diffusivity (lambda(23)), were obtained from each segment. Thus, the distribution maps of these indices along the PYT were obtained. The distribution maps of D(av), FA, and lambda(23) of RNMO patients were significantly different from those of healthy controls, especially in the lower part of the PYT. The differences may be caused by secondary degeneration to lesions in the spinal cord. In conclusion, a length-normalized parameterization method is proposed to establish anatomical correspondence for the PYT. Compared with existed methods, a major merit of our method is to provide comparability across subjects along the PYT on the basis of diffusion tensor tractography and to make it possible for the quantitative analysis along the fiber tract. This method can also be used to quantitatively analyze other white matter fiber tracts between two definite anatomic landmarks in many neurological or psychiatric diseases.

Adult↗

PubMed2006

Diffusion tensor imaging of brain development.

Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral organization and maturation. Diffusion tensor imaging (DTI), a recent magnetic resonance (MR) modality which assesses water diffusion in biological tissues at a microstructural level, has revealed a powerful technique to explore the structural basis of normal brain development. In fact, the tissue organization can be probed non-invasively, and the age-related changes of diffusion parameters (mean diffusivity, anisotropy) reveal crucial maturational processes, such as white matter myelination. Nevertheless, the developing human brain presents several challenges for DTI applications compared with the adult brain. DTI may further be used to detect brain injury well before conventional MRI, as water diffusion changes are an early indicator of cellular injury. This is particularly critical in infants in the context of administration of neuroprotective therapies. Changes in diffusion characteristics further provide early evidence of both focal and diffuse white matter injury in association with periventricular leukomalacia in the preterm infant. Finally, with the development of 3D fiber tractography, the maturation of white matter connectivity can be followed throughout infant development into adulthood with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.

Brain↗

PubMed2002

The quantitation of ADP diffusion gradients across the outer membrane of heart mitochondria in the presence of macromolecules.

We have previously provided evidence that diffusion of metabolites across the porin pores of mitochondrial outer membrane is hindered. A functional consequence of this diffusion limitation is the dynamic compartmentation of ADP in the intermembrane space. These earlier studies were done on isolated mitochondria suspended in isotonic media without macromolecules, in which intermembrane space of mitochondria is enlarged. The present study was undertaken to assess the diffusion limitation of outer membrane in the presence of 10% (w/v) dextran M20, in order to mimic the action of cytosolic macromolecules on mitochondria. Under these conditions, mitochondria have a more native, condensed configuration.Flux-dependent concentration gradients of ADP were estimated by measuring the ADP diffusion fluxes across the porin pores of isolated rat heart mitochondria incubated together with pyruvate kinase (PK), both of which compete for ADP regenerated by mitochondrial creatine kinase (mtCK) within the intermembrane space or by yeast hexokinase (HK) extramitochondrially. From diffusion fluxes and bulk phase concentrations of ADP, its concentrations in the intermembrane space were calculated using Fick's law of diffusion. Flux-dependent gradients up to 23 microM ADP (for a diffusion rate of J(Dif)=1.9 micromol ADP/min/mg mitochondrial protein) were observed. These gradients are about twice those estimated in the absence of dextran and in the same order of magnitude as the cytosolic ADP concentration (30 microM), but they are negligibly low for cytosolic ATP (5 mM). Therefore, it is concluded that the dynamic ADP compartmentation is of biological importance for intact heart cells. If mtCK generates ADP within the intermembrane space, the local ADP concentration can be clearly higher than in the cytosol resulting in higher extramitochondrial phosphorylation potentials. In this way, mtCK contributes to ensure optimal kinetic conditions for ATP-splitting reactions in the extramitochondrial compartment.

Adenosine Diphosphate↗

PubMed2002

Diffusion and convection in collagen gels: implications for transport in the tumor interstitium.

Diffusion coefficients of tracer molecules in collagen type I gels prepared from 0-4.5% w/v solutions were measured by fluorescence recovery after photobleaching. When adjusted to account for in vivo tortuosity, diffusion coefficients in gels matched previous measurements in four human tumor xenografts with equivalent collagen concentrations. In contrast, hyaluronan solutions hindered diffusion to a lesser extent when prepared at concentrations equivalent to those reported in these tumors. Collagen permeability, determined from flow through gels under hydrostatic pressure, was compared with predictions obtained from application of the Brinkman effective medium model to diffusion data. Permeability predictions matched experimental results at low concentrations, but underestimated measured values at high concentrations. Permeability measurements in gels did not match previous measurements in tumors. Visualization of gels by transmission electron microscopy and light microscopy revealed networks of long collagen fibers at lower concentrations along with shorter fibers at high concentrations. Negligible assembly was detected in collagen solutions pregelation. However, diffusion was similarly hindered in pre and postgelation samples. Comparison of diffusion and convection data in these gels and tumors suggests that collagen may obstruct diffusion more than convection in tumors. These findings have significant implications for drug delivery in tumors and for tissue engineering applications.

Biological Transport↗

PubMed2002

Obstructed diffusion in phase-separated supported lipid bilayers: a combined atomic force microscopy and fluorescence recovery after photobleaching approach.

Proteins and other macromolecules are believed to hinder molecular lateral diffusion in cellular membranes. We have constructed a well-characterized model system to better understand how obstacles in lipid bilayers obstruct diffusion. Fluorescence recovery after photobleaching was used to measure the lateral diffusion coefficient in single supported bilayers composed of mixtures of 1,2-dilauroylphosphotidylcholine (DLPC) and 1,2-distearoylphosphotidylcholine (DSPC). Because these lipids are immiscible and phase separate at room temperature, a novel quenching technique allowed us to construct fluid DLPC bilayers containing small disk-shaped gel-phase DSPC domains that acted as obstacles to lateral diffusion. Our experimental setup enabled us to analyze the same samples with atomic force microscopy and exactly characterize the size, shape, and number of gel-phase domains before measuring the obstacle-dependent diffusion coefficient. Lateral obstructed diffusion was found to be dependent on obstacle area fraction, size, and geometry. Analysis of our results using a free area diffusion model shows the possibility of unexpected long-range ordering of fluid-phase lipids around the gel-phase obstacles. This lipid ordering has implications for lipid-mediated protein interactions in cellular membranes.

Cell Membrane↗

PubMed2002

Measurement of the lateral diffusion of human MHC class I molecules on HeLa cells by fluorescence recovery after photobleaching using a phycoerythrin probe.

The mobility of cell surface MHC class I molecules on HeLa cells was measured by fluorescence recovery after photobleaching (FRAP). The probe used for these studies was the phycobiliprotein R-phycoerythrin coupled to Fab fragments of a monoclonal antibody specific for human monomorphic MHC class I molecules. It was found that the recovery curves could be equally well fitted by either a random diffusion model with an immobile component or by an anomalous diffusion model. In the latter case, the anomalous diffusion exponent was consistent with that previously determined by single-particle tracking (SPT) experiments using the same probe (P. R. Smith, I. E. G. Morrison, K. M. Wilson, N. Fernandez, and R. J. Cherry. 1999. Biophys. J. 76:3331-3344). The FRAP experiments, however, yielded a considerably higher value of D(0), the diffusion coefficient for a time interval of 1 s. To determine whether the results were probe dependent, FRAP measurements were also performed with the same monoclonal antibody labeled with Oregon Green. These experiments gave similar results to those obtained with the phycoerythrin probe. FRAP experiments with the lipid probe 5-N-(octadecanoyl) aminofluoroscein (ODAF) bound to HeLa cells gave typical results for lipid diffusion. Overall, our observations and analysis are consistent with anomalous diffusion of MHC class I diffusion on HeLa cells, but quantitative differences between FRAP and SPT data remain to be explained.

Antibodies, Monoclonal↗

PubMed2003

Structural proton diffusion along lipid bilayers.

For H(+) transport between protein pumps, lateral diffusion along membrane surfaces represents the most efficient pathway. Along lipid bilayers, we measured a diffusion coefficient of 5.8 x 10(-5) cm(2) s(-1). It is too large to be accounted for by vehicle diffusion, considering proton transport by acid carriers. Such a speed of migration is accomplished only by the Grotthuss mechanism involving the chemical exchange of hydrogen nuclei between hydrogen-bonded water molecules on the membrane surface, and the subsequent reorganization of the hydrogen-bonded network. Reconstitution of H(+)-binding sites on the membrane surface decreased the velocity of H(+) diffusion. In the absence of immobile buffers, structural (Grotthuss) diffusion occurred over a distance of 100 micro m as shown by microelectrode aided measurements of the spatial proton distribution in the immediate membrane vicinity and spatially resolved fluorescence measurements of interfacial pH. The efficiency of the anomalously fast lateral diffusion decreased gradually with an increase in mobile buffer concentration suggesting that structural diffusion is physiologically important for distances of approximately 10 nm.

Diffusion↗

PubMed2004

Longitudinal diffusion in retinal rod and cone outer segment cytoplasm: the consequence of cell structure.

Excitation signals spread along photoreceptor outer segments away from the site of photon capture because of longitudinal diffusion of cGMP, a cytoplasmic second messenger. The quantitative features of longitudinal diffusion reflect the anatomical structure of the outer segment, known to be profoundly different in rod and cone photoreceptors. To explore how structural differences affect cytoplasmic diffusion and to assess whether longitudinal diffusion may contribute to the difference in signal transduction between photoreceptor types, we investigated, both theoretically and experimentally, the longitudinal diffusion of small, hydrophilic molecules in outer segments. We developed a new theoretical analysis to explicitly compute the longitudinal diffusion constant, Dl, in terms of outer segment structure. Using time-resolved fluorescence imaging we measured Dl of Alexa488 and lucifer yellow in intact, single cones and validated the theoretical analysis. We used numerical simulations of the theoretical model to investigate cGMP diffusion in outer segments of various species. At a given time interval, cGMP spreads further in rod than in cone outer segments of the same dimensions. Across all species, the spatial spread of cGMP at the peak of the dim light photocurrent is 3-5 microm in rod outer segments, regardless of their absolute size. Similarly the cGMP spatial spread is 0.7-1 microm in cone outer segments, independently of their dimensions.

Animals↗