| Perisomatic Feedback Inhibition Underlies Cholinergically Induced Fast Network Oscillations in the Rat Hippocampus In Vitro Neuron, Volume 45, Issue 1, 6 January 2005, Pages 105-117 Edward O. Mann, Jillian M. Suckling, Norbert Hajos, Susan A. Greenfield and Ole Paulsen Summary Gamma frequency network oscillations are assumed to be important in cognitive processes, including hippocampal memory operations, but the precise functions of these oscillations remain unknown. Here, we examine the cellular and network mechanisms underlying carbachol-induced fast network oscillations in the hippocampus in vitro, which closely resemble hippocampal gamma oscillations in the behaving rat. Using a combination of planar multielectrode array recordings, imaging with voltage-sensitive dyes, and recordings from single hippocampal neurons within the CA3 gamma generator, active current sinks and sources were localized to the stratum pyramidale. These proximal currents were driven by phase-locked rhythmic inhibitory inputs to pyramidal cells from identified perisomatic-targeting interneurons. AMPA receptor-mediated recurrent excitation was necessary for the synchronization of interneuronal discharge, which strongly supports a synaptic feedback model for the generation of hippocampal gamma oscillations. Summary | Full Text | PDF (881 kb) |
| Two-Dimensional Determination of the Cellular Ca Binding in Bovine Chromaffin Cells Biophysical Journal, Volume 75, Issue 4, 1 October 1998, Pages 1635-1647 Mohammad Naraghi, Thomas H. Müller and Erwin Neher Abstract The spatiotemporal profile of intracellular calcium signals is determined by the flux of calcium ions across different biological membranes as well as by the diffusional mobility of calcium and different calcium buffers in the cell. To arrive at a quantitative understanding of the determinants of these signals, one needs to dissociate the flux contribution from the redistribution and buffering of calcium. Since the cytosol can be heterogeneous with respect to its calcium buffering property, it is essential to assess this property in a spatially resolved manner. In this paper we report on two different methods to estimate the cellular calcium binding of bovine adrenal chromaffin cells. In the first method, we use voltage-dependent calcium channels as a source to generate calcium gradients in the cytosol. Using imaging techniques, we monitor the dissipation of these gradients to estimate local apparent calcium diffusion coefficients and, from these, local calcium binding ratios. This approach requires a very high signal-to-noise ratio of the calcium measurement and can be used when well-defined calcium gradients can be generated throughout the cell. In the second method, we overcome these problems by using calcium-loaded DM-nitrophen as a light-dependent calcium source to homogeneously and quantitatively release calcium in the cytosol. By measuring [Ca] directly before and after the photorelease process and knowing the total amount of calcium being released photolytically, we get an estimate of the fraction of calcium ions which does not appear as free calcium and hence must be bound to either the indicator dye or the endogenous calcium buffer. This finally results in a two-dimensional map of the distribution of the immobile endogenous calcium buffer. We did not observe significant variations of the cellular calcium binding at a spatial resolution of ∼2m. Furthermore, the calcium binding is not reduced by increasing the resting [Ca] to levels as high as 1.1M. This is indicative of a low calcium affinity of the corresponding buffers and is in agreement with a recent report on the affinity of these buffers (Xu, T., M. Naraghi, H. Kang, and E. Neher. 1997. . . 73:532–545). In contrast to the homogeneous distribution of the calcium buffers, the apparant calcium diffusion coefficient did show inhomogeneities, which can be attributed to restricted diffusion at the nuclear envelope and to rim effects at the cell membrane. Abstract | Full Text | PDF (541 kb) |
| Kinetic Definition of Protein Folding Transition State Ensembles and Reaction Coordinates Biophysical Journal, Volume 91, Issue 1, 1 July 2006, Pages 14-24 Christopher D. Snow, Young Min Rhee and Vijay S. Pande Abstract Using distributed molecular dynamics simulations we located four distinct folding transitions for a 39-residue protein fold. To characterize the nature of each room temperature transition, we calculated the probability of transmission for 500 points along each free energy barrier. We introduced a method for determining transition states by employing the transmission probability, , and determined which conformations were transition state ensemble members (≈0.5). The transmission probability may be used to characterize the barrier in several ways. For example, we ran simulations at 82°C, determined the change in with temperature for all 2,000 conformations, and quantified Hammond behavior directly using correlation. Additionally, we propose that diffusion along may provide the configurational diffusion rate at the top of the barrier. Specifically, given a transition state conformation with estimated =0.5, we selected a large set of subsequent conformations from independent trajectories, each exactly a small time after (250ps). Calculating for the new trial conformations, we generated the (|=250ps) distribution that reflected diffusion. This approach provides a novel perspective on the diffusive nature of a protein folding transition and provides a framework for a quantitative study of activated relaxation kinetics. Abstract | Full Text | PDF (545 kb) |
Copyright © 1972 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 12, Issue 11, 1474-1495, 1 November 1972
doi:10.1016/S0006-3495(72)86176-9
Articles
Rodes Trautman
Theories of diffusion with chemical reaction are reviewed as to their contributions toward developing an algorithm needed for computer simulation of immunodiffusion. The Spiers-Augustin moving sink and the Engelberg stationary sink theories show how the antibody-antigen reaction can be incorporated into boundary conditions of the free diffusion differential equations. For this, a stoichiometric precipitate was assumed and the location of precipitin lines could be predicted. The Hill simultaneous linear adsorption theory provides a mathematical device for including another special type of antibody-antigen reaction in antigen excess regions of the gel. It permits an explanation for the lowered antigen diffusion coefficient, observed in the Oudin arrangement of single linear diffusion, but does not enable prediction of the location of precipitin lines. The most promising mathematical approach for a general solution is implied in the Augustin alternating cycle theory. This assumes the immunodiffusion process can be evaluated by alternating computation cycles: free diffusion without chemical reaction and chemical reaction without diffusion. The algorithm for the free diffusion update cycle, extended to both linear and radial geometries, is given in detail since it was based on gross flow rather than more conventional expressions in terms of net flow. Limitations on the numerical integration process using this algorithm are illustrated for free diffusion from a cylindrical well.