Search PubMed⌕ Search

Biomedical subjects

D Noble

Publications and source records attributed to D Noble.

174 records · Page 10Linked to original sources
PubMed1966

The time and voltage dependence of the slow outward current in cardiac Purkinje fibres.

1. In normal Tyrode solution the initial inward sodium current which is produced in Purkinje fibres in response to a sudden depolarization is followed by a very slow change in current in an outward direction. The magnitude and speed of onset of this slow change both increase with the strength of the depolarization.2. On repolarization, a transient outward current is observed (Deck & Trautwein, 1964). The initial magnitude of this outward current also increases with the strength and duration of the preceding depolarization, with a time course similar to the time course of the slow change in current during depolarization.3. Evidence is presented for the view that the slow change in current during depolarization represents the onset of delayed potassium rectification and that the decline in outward current following repolarization represents its decay.4. Removal of sodium ions greatly increases the threshold of the slow outward current. In the presence of sodium ions 15 mV depolarization is sufficient to produce an appreciable current. In the absence of sodium ions at least 50 mV depolarization is required and, in some fibres, no delayed rectification is observed even when the membrane potential is made positive.5. Prolonged depolarization of the membrane by outward current changes the quiescent membrane potential in a positive direction. This change in potential is attributed to an accumulation of potassium ions in a space immediately outside the cell membrane, which equilibrates slowly with the extracellular fluid. It is shown that this effect is very small during depolarizations of the magnitude and duration of the normal action potential.6. It is concluded that the results are consistent with the view that repolarization of the Purkinje fibre action potential is initiated by a slow increase in K conductance similar to, but much smaller and slower than, that observed in nerve fibres.

Action Potentials↗
PubMed1966

The threshold conditions for initiation of action potentials by excitable cells.

1. The relation between the strength and duration of a just threshold stimulus (strength-duration curve) is analysed for an excitable membrane polarized uniformly and for an excitable cable polarized at one point.2. The effect on the strength-duration curve of non-linearity in the membrane current-voltage curve has been analysed. The strength-duration curve can be derived if the membrane current-voltage relation is independent of time. The effects of changes in the current-voltage curve with time due to the existence of a finite membrane activation time and membrane accommodation are analysed.3. The strength-duration curve for the Hodgkin-Huxley membrane equations (Hodgkin & Huxley, 1952) is compared to that of Hill's (1936) two-time constant model.4. The relation between membrane current-voltage curves and those for a point-polarized cable are derived for the steady-state condition. The cable properties tend to linearize the current-voltage curve and to sharpen the voltage threshold.5. The strength-duration curve for a point-polarized cable whose membrane obeys the Hodgkin-Huxley equations is computed numerically. There is an additional large effect on the cable strength-duration curve arising from the redistribution of charge during passage of a constant current; and the resulting strength-duration curve lies within the range of curves predicted by Hill's model.6. The conditions required for a constant charge threshold (Hodgkin & Rushton, 1946) are shown to be satisfied for short, intense stimuli applied to a cable at one point.7. The results are discussed with reference to the experimental studies available.

Journal Article↗
PubMedDate not supplied

Species difference in sensitivity to ethanol's hedonic effects.

Recent research suggests that rats and mice differ in their sensitivity to ethanol's rewarding effect in the place conditioning paradigm. However, these species have not previously been examined in a comparable manner. The present study compared genetically heterogeneous rats and mice using an identical place conditioning procedure. Each animal received four pairings of a distinctive tactile floor stimulus with injection of ethanol (1.5 g/kg); a different tactile stimulus was paired with saline injection. Ethanol suppressed activity in rats but elevated activity in mice. As in most previous studies with drug-naive animals, rats showed aversion whereas mice showed preference for the ethanol-paired stimulus. This difference cannot be attributed to differences in housing conditions, apparatus, stimuli, or temporal parameters. Rather, it appears to represent a species difference in initial sensitivity to ethanol's hedonic effects. If one assumes that ethanol is both rewarding and aversive, this outcome might be explained by a species difference in tolerance/sensitization, the time-course of the biphasic hedonic response to a single ethanol exposure, or selective association. Together with other recent studies from this laboratory, the present findings suggest the mouse may well be the species of choice for studying preferences conditioned by ethanol.

Animals↗
PubMedDate not supplied

A carbon and nitrogen flux model of mussel digestive gland epithelial cells and their simulated response to pollutants.

The mussel digestive gland epithelial cells provide a key interface between the organism and pollutants such as aromatic hydrocarbons. The simulation of their uptake and export mechanisms as well as an internal protein degradation pathway, and any subsequent disruption to any of them, has been undertaken. A computational model is described, which simulates the flow of carbon and nitrogen through a mussel's digestive cell. The model uses a compartmentalised view of the cell with inviolate 'pipelines' connecting each of the volume-variable partitions. Only the major physiological pathways relevant to the flow of either carbon or nitrogen or volume are modelled. Simulated response to hydrocarbon exposure is examined.

Animals↗
PubMedDate not supplied

The effects of static magnetic field on action potential propagation and excitation recovery in nerve.

Calculations using the Hodgkin-Huxley and one-dimensional cable equations have been performed to determine the expected sensitivity of conduction and refractoriness to changes in the time constant of sodium channel deactivation at negative potentials, as reported experimentally by Rosen (Bioelectromagnetics 24 (2003) 517) when voltage-gated sodium channels are exposed to a 125 mT static magnetic field. The predicted changes in speed of conduction and refractory period are very small.

Action Potentials↗
PubMedDate not supplied

Mechano-electric interactions in heterogeneous myocardium: development of fundamental experimental and theoretical models.

The heart is structurally and functionally a highly non-homogenous organ, yet its main function as a pump can only be achieved by the co-ordinated contraction of millions of ventricular cells. This apparent contradiction gives rise to the hypothesis that 'well-organised' inhomogeneity may be a pre-requisite for normal cardiac function. Here, we present a set of novel experimental and theoretical tools for the study of this concept. Heterogeneity, in its most condensed form, can be simulated using two individually controlled, mechanically interacting elements (duplex). We have developed and characterised three different types of duplexes: (i) biological duplex, consisting of two individually perfused biological samples (like thin papillary muscles or a trabeculae), (ii) virtual duplex, made-up of two interacting mathematical models of cardiac muscle, and (iii) hybrid duplex, containing a biological sample that interacts in real-time with a virtual muscle. In all three duplex types, in-series or in-parallel mechanical interaction of elements can be studied during externally isotonic, externally isometric, and auxotonic modes of contraction and relaxation. Duplex models, therefore, mimic (patho-)physiological mechano-electric interactions in heterogeneous myocardium at the multicellular level, and in an environment that allows one to control mechanical, electrical and pharmacological parameters. Results obtained using the duplex method show that: (i) contractile elements in heterogeneous myocardium are not 'independent' generators of tension/shortening, as their ino- and lusitropic characteristics change dynamically during mechanical interaction-potentially matching microscopic contractility to macroscopic demand, (ii) mechanical heterogeneity contributes differently to action potential duration (APD) changes, depending on whether mechanical coupling of elements is in-parallel or in-series, which may play a role in mechanical tuning of distant tissue regions, (iii) electro-mechanical activity of mechanically interacting contractile elements is affected by their activation sequence, which may optimise myocardial performance by smoothing intrinsic differences in APD. In conclusion, we present a novel set of tools for the experimental and theoretical investigation of cardiac mechano-electric interactions in healthy and/or diseased heterogeneous myocardium, which allows for the testing of previously inaccessible concepts.

Animals↗
PubMedDate not supplied

The effect of compressed air foam on the detection of hydrocarbon fuels in fire debris samples.

In 1998/99 the New Zealand Fire Service implemented compressed air foam delivery systems for the suppression of fires in rural areas. This study investigated whether the introduction of the foam to the seat of the fire created any problems in subsequent analyses of fire debris samples. No significant interferences from the foam were found when the samples were analysed by direct headspace using activated carbon strips. The only foam component detected was limonene.

Air↗
PubMedDate not supplied

An isoprenaline activated sodium-dependent inward current in ventricular myocytes.

In the heart, catecholamines affect pacemaker activity by shifting the activation curve for the nonspecific inward current and increasing both the calcium current, and the delayed potassium current. We report here that in mammalian ventricle there is another mechanism that seems to involve a sodium-dependent inward current. This is elicited by agents that increase intracellular cyclic AMP concentration, such as the beta-adrenergic agonist isoprenaline, and is unaffected by agents which block the three currents listed above, but is absent when external sodium is replaced with tetramethylammonium. Most interestingly, the intracellular pathway(s) linking the beta-receptor(s) to activation of the Ca current and the Na-dependent current, which in both cases presumably involves the intracellular concentration of cAMP, differ, as isoprenaline causes a persistent augmentation of the calcium current whereas the Na-dependent current often fades. These effects of isoprenaline are antagonized by acetylcholine. In unclamped cells, the Na-dependent current depolarizes the membrane to the potential range at which repetitive firing occurs. It may therefore be involved in the generation of ventricular arrhythmias.

Acetylcholine↗
PubMedDate not supplied

Lloyd Roberts memorial lecture. Science, culture and wealth.

1. This lecture defends the view that science, culture and wealth are linked and that, in the long run, the only way to maintain the spirit of excited intellectual enquiry leading to novel exploitable ideas is to attract the young by creating and maintaining a culture in which they respond to the intellectual challenge. 2. The pursuit of science is not independent of the culture in which it develops, nor is it a neutral activity. The objectivity of science neither requires nor entails its neutrality. 3. A comparison between American and British attitudes reveals a major cultural difference that leads otherwise similar political authorities to totally opposed views on the role of public funding of science. 4. The roots of this difference run deep in our culture and have a long history, stretching back at least to the early 19th century and Babbage's Decline of Science campaign. This seems to be a feature of the culture of the governing classes in Britain, at least in modern Britain. The general public perception (revealed by a recent opinion poll) is that more than 80% think that our national prosperity depends on science and technology and that it is important for Britain to be a leading nation in science. 5. The immediate cause of the present political malaise with regard to science funding is the perceived lack of correlation between science expenditure and industrial success in the 1960s. In fact, though, at the micro-economic level, there is a strong correlation between research investment and industrial competitiveness. Those industries that have invested have also succeeded. The general problem lies with a failure of major parts of industry to invest in research rather than in any major weakness or lack of exploitability in British science. 6. It will not solve that problem (which to compare with our main competitors requires an increased civil Research and Development expenditure of 3 pounds billion/annum by British government and industry combined) to try to squeeze funds from the much smaller fundamental science base, nor to impose expensive management structures on university science, which has fluorished in Britain precisely because the "young turks" have been given their head.(ABSTRACT TRUNCATED AT 400 WORDS)

Culture↗