Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum.

Nicholson, Charles; Phillips, J. M.

doi:10.1113/jphysiol.1981.sp013981

Cited by 752 publications

(711 citation statements)

References 68 publications

(100 reference statements)

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“…The data points in Figure 5 reproduce the results of one of the experiments of Nicholson and Phillips (1981). In this experiment, tetramethylammonium (TMA) was ejected from a pipette for a 50-sec period, and the buildup of TMA was monitored at a distance of 114pm.…”

Section: Simulations Of Experimental Resultsmentioning

confidence: 73%

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Model of potassium dynamics in the central nervous system

Odette¹,

Newman

1988

Glia

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A one-dimensional numerical model of potassium dynamics in the central nervous system is developed. The model incorporates the following physiological processes in computing spatial and temporal changes in extracellular K+ concentration, [K+],: 1) the release of K + from K+ sources into extracellular space, 2) diffusion of Kf through extracellular space, 3) active uptake of K + into cells and blood vessels, 4) passive uptake of K+ into a cellular distribution space, and 5) the transfer of K + by K + spatial buffer current flow in glial cells. The following tissue parameters can be specified along the single spatial dimension of the model: 1) the volume fraction and tortuosity of extracellular and glial cell spaces, 2) the volume fraction of the cellular distribution space, 3) rate constants of active uptake and passive uptake processes, and 4) glial cell membrane conductance. The model computes variations in [K+], and current flow through glial cells for three tissue geometries: 1) planar geometry (the retina and the surface of the brain), 2) cylindrical geometry (tissue surrounding a blood vessel), and 3) spherical geometry (tissue surrounding a point source of Kf). For simple sources of K f , the performance of the model matches that predicted from analytical equations. Simulations of previous ion dynamics experiments indicate that the model can accurately predict ion diffusion and K+ current flow in the brain. Simulations of electroretinogram generation and K + siphoning onto blood vessels suggest that unanticipated K' dynamics mechanisms may be operating in the central nervous system.

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Section: Simulations Of Experimental Resultsmentioning

confidence: 73%

“…3A); the gliai simple exponential time course (data not shown). Nicholson and Phillips (1981; Fig. 3, 180 nA).…”

Section: Uptake Processesmentioning

confidence: 96%

Model of potassium dynamics in the central nervous system

Odette¹,

Newman

1988

Glia

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“…[7][8][9] However, because of the inherent invasiveness of the use of exogenous tracers (they have to be introduced into the system of interest), these methods cannot be used to study diffusion in human tissues in vivo. The MR-based measurement of diffusion is fundamentally different from that using tracers: MR is able to utilize endogenous molecules and capable of monitoring the diffusion process itself, i.e.…”

Section: The Diffusion Processmentioning

confidence: 99%

“…This will cause a reduction in the diffusion coefficient of metabolites, as evident from eqns (8) and (9).…”

Section: Diffusion In the Intra-and Extracellular Compartmentsmentioning

confidence: 99%

Diffusion NMR spectroscopy

Nicolay¹,

Braun²,

Graaf³

et al. 2001

NMR in Biomedicine

170

177

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MR offers unique tools for measuring molecular diffusion. This review focuses on the use of diffusionweighted MR spectroscopy (DW-MRS) to non-invasively quantitate the translational displacement of endogenous metabolites in intact mammalian tissues. Most of the metabolites that are observed by in vivo MRS are predominantly located in the intracellular compartment. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. Alternative techniques require the introduction of exogenous probe molecules, which involves invasive procedures, and are also unable to measure molecular diffusion in and throughout intact tissues. The length scale of the process(es) probed by MR is in the micrometer range which is of the same order as the dimensions of many intracellular entities. DW-MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue. In addition, it has been shown that DW-MRS can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders, including ischemia and excitotoxicity of the brain and cancer.

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“…volume that occurs fr om extra-to intracellular fluid (based on an ECF volume of 20%; Nicholson and Phillips, 1981). Only the symmetrical case was con sidered, in that the values for Km and V max for intra-and extracellular fluid were assumed equal.…”

Section: Apparent Kinetics Of Cellular Lactate Transportmentioning

confidence: 99%

In vivo Identification and Quantitative Evaluation of Carrier-Mediated Transport of Lactate at the Cellular Level in the Striatum of Conscious, Freely Moving Rats

Kuhr

Berg

Korf

1988

J Cereb Blood Flow Metab

104

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Summary: Intracerebral dialysis has allowed the contin uous, on-line measurement of lactate in the extracellular fluid (ECF) of conscious, freely moving rats. The rapid time response of the technique allows the direct determi nation of the time course of changes in lactate in ECF following externally imposed stimuli. The time course of lactate appearance in ECF was found to be considerably slower than that observed in tissue following electrocon vulsive shock or during ischemia following cardiac arrest. The ECF data could be fit to an integrated Michaelis Menten model that assumed reversible transport of lac tate across the cell membrane. This transport was found to act only when energy supplies could maintain mem brane integrity and function, since ECF levels of lactateThe intracellular concentration of lactate is di rectly dependent on the cytoplasmic redox state, pH, and the intracellular pyruvate concentration (Hohorst et aI., 1959). Indeed, the cytoplasmic redox state of the brain undergoes dramatic changes following seizure (e.g., Howse and Duffy, 1975) and ischemia (e.g., Lowry et aI., 1964). Since such events produce large changes in the concen trations of lactate, it is important to understand how its intracellular levels are regulated (i.e., via metabolism, transport). Lactate levels are particu larly important in this respect, since intracellular accumulation of lactate is also directly associated with cell dysfunction and death (Myers, 1979; Rehncrona et aI., 1981; Hillered et aI., 1985 848failed to follow tissue levels after cardiac arrest when en ergy resources are depleted. The calculated rate of cel lular lactate transport was two orders of magnitude faster than transport of lactate across the blood-brain barrier in the adult rat, and passive diffusion of lactate was not found to contribute significantly across either cell or blood-brain barriers. Probenecid, an inhibitor of acid transport, was able to block both the efflux of lactate from cell to ECF and the consequent reuptake of lactate by cells in the striatum of the rat following electroconvul sive shock or ischemia.

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Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum.

Cited by 752 publications

References 68 publications

Model of potassium dynamics in the central nervous system

Model of potassium dynamics in the central nervous system

Diffusion NMR spectroscopy

In vivo Identification and Quantitative Evaluation of Carrier-Mediated Transport of Lactate at the Cellular Level in the Striatum of Conscious, Freely Moving Rats

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