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Biomedical subjects

A E McKinnon

Publications and source records attributed to A E McKinnon.

15 recordsLinked to original sources
PubMed2004

A model of magnesium metabolism in young sheep: transactions between plasma, cerebrospinal fluid and bone.

An extension of the previously proposed model of Mg metabolism (Robson et al. 1997) has been developed to consider the transactions of Mg that are associated with cerebrospinal fluid (CSF) and bone. The representation of the CSF as a single MG compartment with uptake from the plasma described by Michaelis-Menten kinetics gives very good agreement with published experiments. Analysis of the available information on resorption of Mg from adult bone indicated that this process makes a negligible contribution to Mg homeostasis and can be omitted from the model.

Animals↗
PubMed2000

CRH-induced electrical activity and calcium signalling in pituitary corticotrophs.

Pituitary corticotroph cells generate repetitive action potentials and associated Ca2+ transients in response to the agonist corticotropin releasing hormone (CRH). There is indirect evidence suggesting that the agonist, by way of complex intracellular mechanisms, modulates the voltage sensitivity of the L-type Ca2+ channels embedded in the plasma membrane. We have previously constructed a Hodgkin-Huxley-type model of this process, which indicated that an increase in the L-type Ca2+ current is sufficient to generate repetitive action potentials (LeBeau et al. (1997). Biophys. J.73, 1263-1275). CRH is also believed to inhibit an inwardly rectifying K+ current. In this paper, we have found that a CRH-induced inhibition of the inwardly rectifying K+ current increases the model action potential firing frequency, [Ca2+]i transients and membrane excitability. This dual modulatory action of CRH on inward rectifier and voltage-gated Ca2+ channels better describes the observed CRH-induced effects. This structural alteration to the model along with parameter changes bring the model firing frequency in line with experimental data. We also show that the model exhibits experimentally observed bursting behaviour, where the depolarization spike is followed by small oscillations in the membrane potential.

Action Potentials↗
PubMed1998

Analysis of a reduced model of corticotroph action potentials.

We have previously described a model for corticotroph plasma membrane electrophysiology [LeBeau et al. (1997). Biophysical Journal 73, 1263-1275]. The model is a Hodgkin-Huxley-like formalism consisting of six coupled ordinary differential equations. Analysis of this model showed that Ca2+ action potentials could be induced by an increase in the L-type voltage-sensitive Ca2+ current. Thus we have demonstrated a putative causal link between an increase in the corticotroph Ca2+ current and action potential generation. We report here the reduction of the model to one with three equations, the behaviour of which was found to correspond well with that of the full model. The reduced model was then subjected to fast-slow subsystem analysis, which revealed the mechanistic interaction between the membrane potential and intracellular Ca2+ concentration that underlies action potential generation. Insights obtained from this analysis were used to investigate experimentally observed aspects of corticotroph electrophysiology such as spontaneous electrical activity, bursting action potentials, and observations from anode break excitation experiments.

Action Potentials↗
PubMed1997

Generation of action potentials in a mathematical model of corticotrophs.

Corticotropin-releasing hormone (CRH) is an important regulator of adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells. The intracellular signaling system that underlies this process involves modulation of voltage-sensitive Ca2+ channel activity, which leads to the generation of Ca2+ action potentials and influx of Ca2+. However, the mechanisms by which Ca2+ channel activity is modulated in corticotrophs are not currently known. We investigated this process in a Hodgkin-Huxley-type mathematical model of corticotroph plasma membrane electrical responses. We found that an increase in the L-type Ca2+ current was sufficient to generate action potentials from a previously resting state of the model. The increase in the L-type current could be elicited by either a shift in the voltage dependence of the current toward more negative potentials, or by an increase in the conductance of the current. Although either of these mechanisms is potentially responsible for the generation of action potentials, previous experimental evidence favors the former mechanism, with the magnitude of the shift required being consistent with the experimental findings. The model also shows that the T-type Ca2+ current plays a role in setting the excitability of the plasma membrane, but does not appear to contribute in a dynamic manner to action potential generation. Inhibition of a K+ conductance that is active at rest also affects the excitability of the plasma membrane.

Action Potentials↗
PubMed1997

A model of magnesium metabolism in young sheep. Magnesium absorption and excretion.

A model of Mg metabolism in sheep is proposed. It is based on standard Michaelis-Menten enzyme kinetics to describe the transport of Mg across the rumen wall and passive diffusion to describe the absorption of Mg in the hindgut. Factors known to have an effect on Mg metabolism in farm animals, namely the concentrations of K and Mg in the diet, and the physico-chemical conditions within the rumen as determined by the type of diet, are incorporated into the model. Consideration of the rumen as the only site of Mg absorption provided an inadequate mechanistic description of Mg metabolism in sheep. To ensure compatibility between predicted Mg absorption and recent independent data sets for Mg balances, it was necessary to include in the model aspects of Mg absorption that operate in the hindgut. The results from this model suggest that there is a need for a series of experiments to determine the important aspects of Mg transport in the hindgut of sheep. Mechanisms of homeostasis are discussed.

Animals↗
PubMed1987

A modeling approach to the estimation of CO diffusing capacity.

Standard methods of measuring the diffusing capacity of the lung for CO are susceptible to inhomogeneity and to errors in the performance of a breathing maneuver by the subject. A mathematical model of CO uptake from a single alveolar lung is developed and used as the basis for an estimation procedure to measure both lung volume and diffusing capacity during a rebreathing maneuver. Because this estimator-model uses the exact flow generated by the subject, errors in such factors as breath-hold times or depth of inspiration do not result. The estimator-model was tested using simulated data from uniformly and nonuniformly ventilated models and was found to be insensitive to noise and inhomogeneity, in contrast to the diffusing capacity of the lungs for CO (exhaled). The estimator-model makes greater use of the available data than traditional methods by utilizing both the slope of the alveolar plateaus for CO and the relative heights of such plateaus in a rebreathing experiment.

Capillaries↗
PubMed1987

Estimation of amount of stationary pulmonary blood from carbon monoxide uptake measurements.

A mathematical model of CO uptake from a single alveolus is modified to include stationary pulmonary blood arising from a pulmonary vascular obstruction. From this model an estimator model is developed that produces simultaneous estimations of the diffusing capacity of the lung for CO and the fraction of the pulmonary capillary blood that is stationary. The estimator model was tested using simulated data from uniform and non-uniform simulators and found to be only mildly sensitive to noise and incorrect values for the pulmonary capillary blood volume. Both the estimator model and breath-to-breath changes in the diffusing capacity of the lung for CO (exhaled) were found to be greatly affected by inhomogeneity of diffusing capacity and ventilation. At times both returned false positive results that limit their use as a screening test for stationary pulmonary blood. Although changes in CO uptake may at times indicate the presence of stationary pulmonary blood, the confounding effects of inhomogeneity of ventilation and diffusing capacity make the use of such changes impractical under most circumstances.

Animals↗
PubMed1984

Characterizing and correcting for the dynamic response of a bag-in-box system.

A bag-in-box system (BBS) whose volume is monitored by a mechanical spirometer tends to have a slow response if the volume of the box is large, and this may significantly affect its measurement of gas flow. We describe a device for creating reproducible gas flows with which the impulse response of a BBS may be conveniently determined. Two computational techniques for correcting a BBS flow measurement for the effects of the impulse response were investigated: 1) an exponential model method that assumes a second-order model of the BBS dynamics and 2) a Fourier transform-based method of deconvolution known as Wiener filtering. Both correction methods produced a significant increase in the accuracy of BBS flow estimations, with the Wiener filter giving superior results.

Respiratory Function Tests↗
PubMed1983

Correcting for the dynamic response of a respiratory mass spectrometer.

Mass spectrometers produce distorted measurements of gas concentrations because of the time delays and rise times inherent in their responses. Three techniques for numerically correcting such distortion were applied to the acetylene step responses of a Perkin-Elmer MGA1100 mass spectrometer and to simulated data. The techniques investigated were 1) a simple time-delay correction, 2) an exponential model method that assumes a biexponential form for the peak of the impulse response, and 3) a Fourier transform method of deconvolution known as Wiener filtering. The time-delay correction produced an order of magnitude reduction in measurement error. The exponential model method improved on the time-delay correction, and the Wiener filter gave the most accurate corrections in all cases examined.

Fourier Analysis↗
PubMed1982

Teaching the uptake and distribution of halothane. A computer simulation program.

A computer aided learning program for teaching the kinetics of uptake and distribution of the inhalational anaesthetic halothane is described. The program is based on a seven-compartment model which simulates the action of halothane on ventilation and on the cardiovascular system. The program is available to the student in four forms: one with no changes in circulation or respiration, one with the cardiovascular effects of halothane included, one with respiratory effects only, and one with both of these effects combined. The student can study the importance of the influence of halothane on respiration and blood circulation by comparing results from simulations on different models. The simulation is presented as graphs which are continuously displayed on an alphanumeric visual display terminal. Interaction with the program is possible at all times to change the simulation speed, the variables being graphed, the inspired halothane fraction, and the fresh gas flow.

Anesthesia, Inhalation↗
PubMed1982

Evaluation of a computer simulation program for teaching halothane uptake and distribution.

A pilot evaluation of a simulation program used during a tutorial for the teaching of uptake and distribution of the inhalational anaesthetic halothane shows a highly significant improvement in the students' answers after the tutorial using a 'before and after' questionnaire. The students showed an understanding of the program's display and model limitations. This encourages the further use of the program.

Anesthesiology↗
PubMed1981

The extent of reflux of unconjugated 14C-cholic acid from the liver in subjects with normal liver function.

An improved understanding of bile acid physiology is a prerequisite for the construction of an acceptable model for describing plasma clearance of bile acids. The aim of this study was to determine the extent of reflux unconjugated cholic acid from the liver to the plasma in subjects with normal liver function. The clearance of a bolus injection of unconjugated 14C-cholic acid was studied in four subjects using samples collected simultaneously from a peripheral and a hepatic vein. Hepatic extraction ratios calculated directly from the data were found to be essentially constant during the 20 min following injection, with average values of 0.60-0.72. This indicates that reflux did not occur significantly in the subjects investigated. These results are interpreted as favouring a model in which exchange of unconjugated 14C-cholic acid occurs between the plasma and a peripheral compartment with final removal from the plasma to the liver.

Carbon Radioisotopes↗