Biomedical subjects

W G Gibson

Publications and source records attributed to W G Gibson.

35 records · Page 2Linked to original sources

PubMed1997

Quantal currents and potential in the three-dimensional anisotropic bidomain model of smooth muscle.

The potential generated in the smooth muscle of the vas deferens on release of a quantum of transmitter from a varicosity was analyzed using a three-dimensional bidomain continuum model. Current was injected at the origin of the bidomain; this current had the temporal characteristics of the junctional current. The membrane potential, intracellular potential, and extracellular potential, as well as the extracellular current, were then calculated throughout the bidomain at different times. Calculations were performed to show the effect of changing the anisotropy ratios of the intracellular and extracellular conductivities on the spread of current and potential in each of the three dimensions. These results provide a theoretical framework for ascertaining the time course of transmitter interaction at a varicosity following the secretion of a quantum of transmitter.

Animals↗

PubMed1997

Probabilistic secretion of quanta and the synaptosecretosome hypothesis: evoked release at active zones of varicosities, boutons, and endplates.

A quantum of transmitter may be released upon the arrival of a nerve impulse if the influx of calcium ions through a nearby voltage-dependent calcium channel is sufficient to activate the vesicle-associated calcium sensor protein that triggers exocytosis. A synaptic vesicle, together with its calcium sensor protein, is often found complexed with the calcium channel in active zones to form what will be called a "synaptosecretosome." In the present work, a stochastic analysis is given of the conditions under which a quantum is released from the synaptosecretosome by a nerve impulse. The theoretical treatment considers the rise of calcium at the synaptosecretosome after the stochastic opening of a calcium channel at some time during the impulse, followed by the stochastic binding of calcium to the vesicle-associated protein and the probability of this leading to exocytosis. This allows determination of the probabilities that an impulse will release 0, 1, 2,... quanta from an active zone, whether this is in a varicosity, a bouton, or a motor endplate. A number of experimental observations of the release of transmitter at the active zones of sympathetic varicosities and boutons as well as somatic motor endplates are described by this analysis. These include the likelihood of the secretion of only one quantum at an active zone of endplates and of more than one quantum at an active zone of a sympathetic varicosity. The fourth-power relationship between the probability of transmitter release at the active zones of sympathetic varicosities and motor endplates and the external calcium concentration is also explained by this approach. So, too, is the fact that the time course of the increased rate of quantal secretion from a somatic active zone after an impulse is invariant with changes in the amount of calcium that enters through its calcium channel, whether due to changes consequent on the actions of autoreceptor agents such as adenosine or to facilitation. The increased probability of quantal release that occurs during F1 facilitation at the active zones of motor endplates and sympathetic boutons is predicted by the residual binding of calcium to a high-affinity site on the vesicle-associated protein. The concept of the stochastic operation of a synaptosecretosome can accommodate most phenomena involving the release of transmitter quanta at these synapses.

Action Potentials↗

PubMed1997

Synaptic transmission at visualized sympathetic boutons: stochastic interaction between acetylcholine and its receptors.

Excitatory postsynaptic currents (EPSCs) were recorded with loose patch electrodes placed over visualized boutons on the surface of rat pelvic ganglion cells. At 34 degrees C the time to peak of the EPSC was about 0.7 ms, and a single exponential described the declining phase with a time constant of about 4.0 ms; these times were not correlated with changes in the amplitude of the EPSC. The amplitude-frequency histogram of the EPSC at individual boutons was well described by a single Gaussian-distribution that possessed a variance similar to that of the electrical noise. Nonstationary fluctuation analysis of the EPSCs at a bouton indicated that about 120 ACh receptor channels were available beneath boutons for interaction with a quantum of ACh. The characteristics of these EPSCs were compared with the results of Monte Carlo simulations of the quantal release of 9000 acetylcholine (ACh) molecules onto receptor patches of density 1400 microns-2 and 0.41 micron diameter, using a kinetic scheme of interaction between ACh and the receptors similar to that observed at the neuromuscular junction. The simulated EPSC generated in this way had temporal characteristics similar to those of the experimental EPSC when either the diffusion of the ACh is slowed or allowance is made for a finite period of transmitter release from the bouton. The amplitude of the simulated EPSC then exhibited stochastic fluctuations similar to those of the experimental EPSC.

Acetylcholine↗

PubMed1996

Quantal transmitter release onto different patterns of receptor distributions at somatic neuromuscular junctions.

The effect of different distributions of acetylcholine receptors at the active zone of somatic motor-nerve terminals on the amplitude-frequency histogram of spontaneous excitatory currents due to the secretion of a quantum transmitter has been analysed by numerically solving the diffusion and binding equations. The time course and amplitude of the spontaneous currents of different arrangements of receptors has been determined. Organization of receptors into stripes of different patterns beneath the active zone, which is known to occur, does not affect the amplitude or temporal characteristics of the spontaneous currents. Increases in the amount of transmitter in a quantum released onto the stripes does not introduce any subunit structure into the spontaneous currents. It is concluded that if subunits are detectable in measured amplitude-frequency histograms of spontaneous potentials they arise because of presynaptic rather than postsynaptic factors.

Action Potentials↗

PubMed1996

Quantal transmitter release at somatic motor-nerve terminals: stochastic analysis of the subunit hypothesis.

Here we analyze the problem of determining whether experimentally measured spontaneous miniature end-plate currents (MEPCs) indicate that quanta are composed of subunits. The properties of MEPCs at end plates with or without secondary clefts at the neuromuscular junction are investigated, using both stochastic and deterministic models of the action of a quantum of transmitter. It is shown that as the amount of transmitter in a quantum is increased above about 4000 acetylcholine (ACh) molecules there is a linear increase in the size of the MEPC. It is possible to then use amplitude-frequency histograms of such MEPCs to detect a subunit structure, as there is little potentiation effect above 4000 ACh molecules. Autocorrelation and power spectral analyses of such histograms establish that their subunit structure can be detected if the coefficient of variation of the subunit size is less than about 0.12 or, if electrical noise is added, about 0.1. Positive gradients relate the rise time and half-decay times of MEPCs to their amplitude, even in the absence of potentiating effects; these gradients are shallower at motor nerve terminals that possess secondary clefts. The effect of asynchronous release of subunits is also investigated. The criteria determined by this analysis for identifying a subunit composition in the quantum are applied to an amplitude-frequency histogram of MEPCs recorded from a small group of active zones at a visualized amphibian motor-nerve terminal. This did not provide evidence for a subunit structure.

Acetylcholine↗

PubMed1995

Quantal transmission at purinergic synapses: stochastic interaction between ATP and its receptors.

Monte Carlo methods are used to analyze the stochastic interaction between ATP, released in a packet at a bouton, and the underlying patch of purinoceptors. The time-course of the average quantal current recorded with an intracellular electrode in the peripheral and central nervous systems is reconstructed, given the geometry of the synapse and the known kinetics of ATP action. This leads to certain restrictions on the possible numbers of ATP molecules in a quantum and the density of purinoceptors at the synapses. The addition of an ectoenzyme into the synaptic cleft with the known kinetics of ATPase gives rise to a quantal current of appropriate time-course if the number of ATP molecules in a quantum is increased over that in the absence of the ATPase. The stochastic variability in the quantal current is less than 0.1 for a given size quantum.

Adenosine Triphosphate↗

PubMed1995

On the contribution of quantal secretion from close-contact and loose-contact varicosities to the synaptic potentials in the vas deferens.

A bidomain model of the smooth muscle syncytium has been used to analyse the sources of transmitter secretion that give rise to the excitatory junction potential (EJP) in the guinea-pig vas deferens. The timecourse of the spontaneous excitatory junction potential (SEJP) has been taken to be the same as the time course of action of a quantum of transmitter. The amplitude of the SEJP is dependent on both the size of the quantum secreted and the distance away of the source of the quantum from the muscle cells. Two such sources are considered, one identified as the close-contact varicosities (CCVS) about 50 nm from the muscle and the other as loose-contact varicosities (LCVS) at greater distances. It is shown that in order for the syncytium to reach equipotential by the time the EJP has declined to about 80% of its peak, each muscle cell must receive a quantum of transmitter. The relatively low density of innervation of muscle cells by CCVS so far reported, together with the extremely low probability for secretion from these, indicates that many LCVS surrounding each muscle cell contribute to the EJP. The rising phase of the EJP contains components that indicate the sources of the transmitter responsible for its generation, and these components have been made explicit by differentiating the EJP to give the DEJP. This always has a smooth and relatively slow component that lasts for about 80 to 100 ms and occasionally has fast components superimposed on it. These latter are shown to be almost certainly due to secretion of quanta from the CCVS. It is known that there is a distribution of action potential velocities in the sympathetic nerves to the vas deferens. To account for this, the secretion of quanta from different CCVS on a set of muscle cells in the syncytium were given different delays so that the DEJP consisted of a slow wave form that extended over 80 ms, composed of clearly discernible components arising from the CCVS. This wave form could be smoothed by allowing each cell in the syncytium to receive a quantum of transmitter from a CCV, a condition that did not then allow for the appearance of fast components in the DEJP. A model that generated both the non-intermittent slow component of the DEJP and the intermittent fast component consisted of each cell in the syncytium receiving an innervation from a single CCV as well as from a large number of LCVS. In this case, all the varicosities could secrete a quantum of transmitter with a particular probability after a delay characteristic for that varicosity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic Fibers↗

PubMed1995

Electrotonic coupling between two CA3 hippocampal pyramidal neurons: a distributed cable model with somatic gap-junction.

A model of a pair of electrotonically coupled CA3 hippocampal pyramidal neurons is presented. Each neuron is represented by a tapered equivalent cable attached to an isopotential soma. The synaptic potential in a neuron soma is determined as a consequence of electrical coupling to another soma that receives a synaptic input on its dendritic tree. Estimates of the coupling resistances, soma input resistances and soma-to-dendritic tree conductance ratio show that a substantial current may arise in a neuron as a consequence of synaptic activity in a neuron coupled to it. The small increase in decay time due to coupling in the model indicates that actual coupling is between more than just pairs of neurons.

Animals↗

PubMed1995

Probabilistic secretion of quanta: spontaneous release at active zones of varicosities, boutons, and endplates.

The amplitude-frequency histogram of spontaneous miniature endplate potentials follows a Gaussian distribution at mature endplates. This distribution gives the mean and variance of the quantum of transmitter. According to the vesicle hypothesis, this quantum is due to exocytosis of the contents of a single synaptic vesicle. Multimodal amplitude-frequency histograms are observed in varying degrees at developing endplates and at peripheral and central synapses, each of which has a specific active zone structure. These multimodal histograms may be due to the near synchronous exocytosis of more than one vesicle. In the present work, a theoretical treatment is given of the rise of intraterminal calcium after the stochastic opening of a calcium channel within a particular active zone geometry. The stochastic interaction of this calcium with the vesicle-associated proteins involved in exocytosis is then used to calculate the probability of quantal secretions from one or several vesicles at each active zone type. It is shown that this procedure can account for multiquantal spontaneous release that may occur at varicosities and boutons, compared with that at the active zones of motor nerve terminals.

Animals↗

PubMed1995

Quantal transmission at purinergic junctions: stochastic interaction between ATP and its receptors.

The time course of most quantal currents recorded with a small diameter electrode placed over visualized varicosities of sympathetic nerve terminals that secrete ATP was determined: these had a time to reach 90% of peak of 1.3-1.8 ms and a time constant of decay of 12-18 ms; they were unaffected by blocking ectoenzymes or the uptake of adenosine. Monte Carlo methods were used to analyze the stochastic interaction between ATP, released in a packet from a varicosity, and the underlying patch of purinoceptors, to reconstitute the time course of the quantal current. This leads to certain restrictions on the possible number of ATP molecules in a quantum (about 1000) and the density of purinoceptors at the junctions (about 1000 microns-1), given the known geometry of the junction and the kinetics of ATP action. The observed quantal current has a relatively small variability (coefficient of variation < 0.1), and this stochastic property is reproduced for a given quantum of ATP. Potentiation effects (of about 12%) occur if two quanta are released from the same varicosity because the receptor patch is not saturated even by the release of two quanta. The simulations show that quantal currents have a characteristically distinct shape for varicosities with different junctional cleft widths (50-200 nm). Finally, incorporation of an ectoenzyme with the known kinetics of ATPase into the junctional cleft allows for a quantal current of the observed time course, provided the number of ATP molecules in a quantum is increased over the number in the absence of the ATPase.

Adenosine Triphosphatases↗

PubMed1994

Dynamics of the CA3 pyramidal neuron autoassociative memory network in the hippocampus.

A theory for the dynamics of sparse associative memory has been applied to the CA3 pyramidal recurrent network in the hippocampus. The CA3 region is modelled as a network of pyramidal neurons randomly connected through their recurrent collaterals. Both the elliptical spread of the axonal systems and the exponential decrease in connectivity with distance are taken into account in estimating the connection probabilities. Pyramidal neurons also receive connections from inhibitory interneurons which occur in large numbers throughout the network; these in turn receive inputs from other inhibitory interneurons and from pyramidal neurons. These inhibitory neurons are modelled as rapidly acting linear devices which produce outputs proportional to their inputs; they perform an important regulatory function in the setting of the membrane potentials of the pyramidal neurons. The probability of a neuron firing in a stored memory, which determines the average number of neurons active when a memory is recalled, can be set at will. Memories are stored at the recurrent collateral synapses using a two-valued Hebbian. Allowance is made in the theory both for the spatial correlations between the learned strengths of the recurrent collateral synapses and temporal correlations between the state of the network and these synaptic strengths. The recall of a memory begins with the firing of a set of CA3 pyramidal neurons that overlap with the memory to be recalled as well as the firing of a set of pyramidal neurons not in the memory to be recalled; the firing of both sets of neurons is probably induced by synapses formed on CA3 neurons by perforant pathway axons. The firing of different sets of pyramidal neurons then evolves by discrete synchronous steps. The CA3 recurrent network is shown to retrieve memories under specific conditions of the setting of the membrane potential of the pyramidal neurons by inhibitory interneurons. The adjustable parameters in the theory have been assigned values in accord with the known physiology of the CA3 region. Certain levels of overlap between the input and the memory to be retrieved must also be satisfied for almost complete retrieval. The number of memories which can be stored and retrieved without degradation is primarily a function of the number of active neurons when a memory is recalled and the degree of connectivity in the network. The inhomogeneity in the connectivity of the pyramidal cells improves both capacity and overlap of the final state with the memory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Principles and design feasibility of a Doppler ultrasound intravascular volumetric flowmeter.

A new Doppler ultrasound intravascular method is described for the measurement of volumetric flow. Based on the principles described by Hottinger and Meindl [15], it uses a novel semispherical transducer mounted at the tip of a catheter, which generates sample volumes in the form of a thin semispherical shell. Volumetric flow is calculated by using the average velocity determined from the received Doppler spectrum and the area of intersection of a sample volume that completely intersects flow across the vessel. Although a catheter-size transducer was not developed, a larger version was tested using an in vitro steady flow model. Maximum average flow error was limited to 9% for steady flows of 2 to 7 L/min. This error is believed to be a result of the nonuniform intensity generated by the prototype transducer, as well as slight variations in the received power, rather than any fundamental limitations of the flow measurement method itself. Since this study has verified the design principles and feasibility of this new approach, we believe that more detailed experimental investigations are warranted.

Adult↗

PubMed1993

Extracellular current flow and potential during quantal transmission from varicosities in a smooth muscle syncytium.

A discrete model has been developed that describes the extracellular current that flows in a smooth muscle syncytium upon the secretion of a quantum of transmitter onto a smooth muscle cell in the syncytium. This allows a description to be given of the current (called the excitatory junctional current (EJC)) recorded by an electrode of given diameter placed on the surface of the muscle, during synaptic transmission from a varicosity situated anywhere in the muscle. The EJC is of maximum negative amplitude when the varicosity is at the surface of the muscle near the inside rim of the electrode and decreases as the varicosity moves to the centre of the electrode. It is of maximum positive amplitude when the varicosity is at the surface near the outside rim of the electrode and declines rapidly in amplitude as the varicosity is removed further from the outside rim. Smaller diameter electrodes give larger EJCs than larger diameter electrodes for most positions of the varicosity on the surface of the muscle. The EJC amplitude declines for varicosities beneath the electrode that are not on the surface of the muscle, but deep in the tissue. The rate of this decline is greater the smaller the diameter of the electrode. The time-course of the EJC is largely invariant under changes in the position of the varicosity with respect to the recording electrode. Changes in the polarity of the current flow during a single EJC can occur, however, if two varicosities secrete transmitter simultaneously, one inside the electrode and one outside, and the time-course of the currents due to the individual varicosities is either the same or slightly different. This theoretical work has been used to interpret a number of recent experimental studies of extracellular current flow during autonomic neuromuscular transmission.

Animals↗

PubMed1991

Probabilistic secretion of quanta in the central nervous system: granule cell synaptic control of pattern separation and activity regulation.

The implications of probabilistic secretion of quanta for the functioning of neural networks in the central nervous system have been explored. A model of stochastic secretion at synapses in simple networks, consisting of large numbers of granule cells and a relatively small number of inhibitory interneurons, has been analysed. Such networks occur in the input to the cerebellum Purkinje cells as well as to hippocampal CA3 pyramidal cells and to pyramidal cells in the visual cortex. In this model the input axons terminate on granule cells as well as on an inhibitory interneuron that projects to the granule cells. Stochastic secretion at these synapses involves both temporal variability in secretion at single synapses in the network as well as spatial variability in the secretion at different synapses. The role of this stochastic variability in controlling the size of the granule cell output to a level independent of the size of the input and in separating overlapping inputs has been determined analytically as well as by simulation. The regulation of granule-cell output activity to a reasonably constant value for different size inputs does not occur in the absence of an inhibitory interneuron when both spatial and temporal stochastic variability occurs at the remaining synapses; it is still very poor in the presence of such an interneuron but in the absence of stochastic variability. However, quite good regulation is achieved when the inhibitory interneuron is present with spatial and temporal stochastic variability of secretion at synapses in the network. Excellent regulation is achieved if, in addition, allowance is made for the nonlinear behaviour of the input-output characteristics of inhibitory interneurons. The capacity of granule-cell networks to separate overlapping patterns of activity on their inputs is adequate, with spatial variability in the secretion at synapses, but is improved if there is also temporal variability in the stochastic secretion at individual synapses, although this is at the expense of reliability in the network. Other factors which improve pattern separation are control of the output to very low activity levels, and a restriction on the cumulative size of the excitatory input terminals of each granule cell. Application of the theory to the input neural networks of the cerebellum and the hippocampus shows the role of stochastic variability in quantal transmission in determining the capacity of these networks for pattern separation and activity regulation.

Animals↗

PubMed1986

Stress analysis of vasoconstriction at arterial branch sites.

The object of the research was to estimate wall stresses caused by vasoconstriction at arterial branches. The basic procedure was a combination of experimental strain measurement and analytical stress analysis. Segments of canine renal arteries were perfused and stimulated to constrict with dopamine hydrochloride and norepinephrine. Surface wall deformation was measured with a stereo-photographic technique. A plane stress finite element analysis was used to calculate wall stresses based on the experimentally derived deformations. The major result of the study was to demonstrate tensile stresses, and in some cases biaxial tension, in contracting vessels. Peak stresses in the apex of the acute angle of the branches were approximately three times unpenetrated hoop stress in the parent vessels. The results imply that constriction at a branch site may be capable of generating sufficient wall tension to tear arterial tissue, and that smooth muscle reactivity is important with respect to the etiology of cerebral aneurysms and the clinical management of acute branch site pathology.

Animals↗

PubMed1982

Age-associated C-cell hyperplasia in the human thyroid.

C cells in 26 normal human thyroids from forensic autopsies were identified by immunoperoxidase staining for calcitonin. C-cell concentrations and total C-cell numbers were determined with the use of morphometric techniques. There was great variation in C-cell density within a given gland and among individuals, although C cells tended to concentrate about one third of the way down the vertical axis of the lateral lobes. Densities of 1-2000 cells/cu mm were found in the third and later decades. In addition there was a statistically significant (P less than 0.01) positive Spearman correlation between total C-cell numbers and age in males. C-cell hyperplasia appears to be an age-related phenomenon that may have physiologic significance and must be taken into consideration in evaluation of thyroid glands for the diagnosis of premalignant lesions of C cells.

Adolescent↗

PubMed1980

Multiple coronary artery dissections in old age. A unique case.

A 70-year-old man died of alcoholic cirrhosis and long-standing pulmonary emphysema. Multiple independent dissecting aneurysms involved the distal epicardial branches of the right and left coronary arteries, but spared their proximal trunks. These dissections extended distally from vascular branch points in association with acute and chronic medionecrosis. Iatrogenic trauma superimposed on preexisting medial weakness may have accounted for what is, to our knowledge, a unique presentation of a rare condition.

Aged↗