Thesis--University of Alabama. / Includes bibliography.

Thesis (PhD)-Open University. BLDSC no.DX94698.

Thesis--University of Florida. / Description based on print version record. Typescript. Vita. Includes bibliographical references (leaves 79-86).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--Brigham Young University. Dept. of Communication Disorders, 2007. / Includes bibliographical references (p. 59-63).

No description available.

Application of 5-hydroxytryptamine induces a voltage-dependent inward current in voltage clamped C1 neurones of Helix aspersa. This response has been shown to be the result of a decrease in K conductance and was studied using patch clamp and voltage clamp techniques. Single channel K currents were recorded from cell-attached patches of the C1 neurone. Two sizes of unitary outward currents were commonly observed. The I-V relationships of both these unitary currents could be fitted by the Goldman-Hodgkin-Katz equation for a K current, having slope conductances of around 14pS and 54pS at +10mV, patch potential. Experiments, altering the K concentration in the patch pipette, or on the outer surface of isolated outside-out patches, suggested that these unitary currents were due to the flow of K+ ions. Application of 5-hydroxytryptamine onto the C1 neurone, from out with the patch pipette, reduced the activity of the larger K channels, recorded in the cell-attached patch. Both Ca-dependent, and Ca-independent K channels were observed on isolated inside-out membrane patches. It was unclear which of these types of channel corresponded to the 5-hydroxytryptamine sensitive channel in the cell-attached patch. Voltage clamp experiments also gave confusing results regarding the Ca-dependency of the 5-hydroxytryptamine response. However, in some C1 neurones 5-hydroxytryptamine caused a flattening of the "N" shaped I-V relationship, suggesting a decrease in the Ca-dependent outward current. The possibility that more than one type of K current was suppressed by 5-hydroxytryptamine was considered. The effect of phosphodiesterase inhibitors was consistent with a mediation of the 5-hydroxytryptamine response by cyclic nucleotides. Injection of cAMP induced an inward current in the C1 neurone. Single channel outward currents, which reversed at -50mV, were recorded from the A neurone. The activity of these channels was increased by 5-hydroxytryptamine, but their ionic nature was uncertain. Unitary outward currents of the M neurone were also recorded.

Possible sources of electrical transmembrane potentials in living cells are examined. The equations of Nernst, Ussing and Goldman cannot predictively explain the origin of membrane potential because they all require knowledge of concentrations of ions both outside and inside the cell, and these internal concentrations are themselves generated by activity of the cell. Therefore a new electrochemical theory for the steady state has been developed, which takes into account both active transport and the Donnan effect. The theory, which should be general to all living cells, successfully predicts membrane potential in examples examined. Certain hitherto unknown effects have been predicted, the most important of which have been named (a) the "nebenion effect", whereby the presence of other ionic species of the same charge sign as the actively transported ionic species depresses membrane potential, and (b) the "Donnan enhancement effect", whereby the membrane potential when both active transport and a Donnan system co-exist is greater than the sum of the potentials produced by each acting separately. Two important consequences follow ; (i) It is impossible for hydrogen or hydroxyl ion transport to generate a significant membrane potential in the face of environmental concentrations of nebenions. Thus the potential found across any membrane must be due to transport of majority ionic species and/or Donnan effects. (ii) The membrane potential in animal cells can only be explained by the "Donnan enhancement effect" in face of the "nebenion effect". Double Donnan systems and both linked and twin independent transports of two ionic species are considered. The effect of fixed charge either in the cell wail or as 3-potential on either side of the membrane is examined. Experimental procedures for the measurement of membrane potential are examined and a new integral microscope- manipulator system design is presented. Investigations are described of causes, and ways of avoiding, artefacts in measurements with micropipette electrodes, by studies both on model systems and directly on maize root cells. Experimental techniques for the measurement of cell membrane resistance and capacity are reviewed, and a new method is introduced to produce AF impedance spectra of cells, from which both membrane resistance and capacity can be calculated. The electronic system used a phase-sensitive detector to simplify analysis of the a.c. bridge network, as well as to remove noise. It is believed this was in 1973 the first use of such a system in electrophysiology. The technique was tested on dummy circuits to represent the living cell. The properties of micropipette electrodes were investigated. Membrane resistance and capacity were successfully measured in maize root cells. This new technique makes these measurements possible on smaller cells than hitherto, since it uses a lone single-barrelled microelectrode. Finally the significance of such measurements in terms of cell and tissue anatomy is considered, and the theory of "vergence" resistance of small connecting bridges between cells is extended to cover the multiperforate septum.

The aim of this thesis was to investigate the potential use of hydrogen-bonded organic semiconductors in photostimulation of mammalian cells and the determination of the mechanism thereof.

When modelling tissue-level cardiac electrophysiology, a continuum approximation to the discrete cell-level equations, known as the bidomain equations, is often used to maintain computational tractability. The bidomain equations are derived from the discrete equations using a mathematical technique known as homogenisation. As part of this derivation conductivity tensors are specified for use in the continuum model. Analysing the derivation of the bidomain equations allows us to investigate how microstructure, in particular gap junctions that electrically connect cells, affect tissue-level conductivity properties and model solutions. We perform two distinct but related strands of investigation in this thesis. In the first, we consider the effect of including gap junctions on the results of both discrete and continuum simulations, and identify when the continuum model fails to be a good approximation to the discrete model. Secondly, we perform a comprehensive study into how cell-level microstructure properties, such as cell shape, impact the homogenised conductivities to be used in a tissue-level continuum model. This will allow us to predict how the onset of a disease or a change in cellular microstructure will affect the propagation of action potentials. To do this, we first derive a modified version of the bidomain equations that explicitly takes gap junctions into account. We then derive analytic solutions for the homogenised conductivity tensors on a simplified two-dimensional geometry and find that diseased gap junctions have a large impact on the results of homogenisation. On this same geometry we compare the results of discrete and continuum simulations and find a significant discrepancy between model conduction velocities when we introduce gap junctions with lower coupling strength, or when we consider elongated cells. From this, we conclude that the bidomain equations are less likely to give an accurate representation of the underlying discrete system when modelling diseased states whose symptoms include reduced gap junction coupling or an increase in myocyte length. We then use a more realistic two-dimensional geometry and numerically approximate the homogenised conductivity tensors on this geometry. We discover that the packing of cells has a substantial effect on conduction, with a brick-wall geometry particularly beneficial for fast propagation, and that gap junctions also have a large effect on conduction. Finally, we consider a three-dimensional cellular geometry and show that the effect of changing gap junction properties is different when compared to two dimensions, and discover that the anisotropy ratios of the tissue are highly sensitive to changes in gap junction parameters. Overall, we conclude that gap junctions and cell structure have a large effect on discrete and continuum model results, and on homogenised conductivity calculations in tissue-level cardiac electrophysiology.