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L Farnell

Publications and source records attributed to L Farnell.

9 recordsLinked to original sources
PubMed1998

On the origin of skewed distributions of spontaneous synaptic potentials in autonomic ganglia.

The histograms of spontaneous synaptic potentials at synapses in autonomic ganglia are described by distributions consisting of mixtures of Gaussians, rather than by single Gaussian distributions. The possible origin of these mixed distributions is investigated, using Monte-Carlo simulations of the action of spontaneously released units of transmitter. A single unit of acetylcholine of fixed size, released from an active zone with receptor patches both beneath and adjacent to the zone, does not give rise to the observed histograms. But if the unit is of variable size, consisting of integer multiples of smaller units, and release is from an active zone onto either the receptor patch beneath, or in addition onto adjacent patches, then the histogram is well described by a mixture of Gaussians. However, this explanation is unlikely to be correct as present evidence suggests that in most cases the released unit of transmitter saturates the postsynaptic receptor patch beneath the active zone. The final case considered is where a unit of transmitter is spontaneously released from an active zone, simultaneously with a unit in an adjacent zone less than one micron away. The histogram of potentials then conforms to those observed even when there are differences in the sizes of the receptor patches. It is suggested that this kind of release could provide an explanation for distributions of spontaneous potentials that are mixtures of Gaussians.

Animals↗
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

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

MULTICOMP: a program for preparing sequence data for phylogenetic analysis.

MULTICOMP is a program that assists in the phylogenetic analysis of DNA sequences. It streamlines sequence handling and analysis. Input is from either individual sequence files or a file of aligned sequences. It produces data on variation at DNA and amino acid sequence level and can also convert sequences to data formats suitable for PHYLIP, PAUP and MacClade phylogenetic inference programs. Further, two tree-building programs, NEIGHBOR and DNAPARS, of PHYLIP can be directly run from within it. MULTICOMP performs Sawyer's algorithm for detection of gene conversion. The program facilitates analysis using only part of the data of a data set or using two or more combined data sets.

Algorithms↗
PubMed1975

Conformation of histamine derivatives. 5. Molecular orbital calculation of the H1-receptor "essential" conformation of histamine.

Conformational energies of histamine and 4-methylhistamine monocations are calculated using the EHT molecular orbital procedure; the results are expressed as potential energy surfaces in which bond rotations (theta1 for ring-Cbeta, theta2 for Cbeta-Calpha) are measured along the axes, and energy variation is indicated by contours. Using the classical Boltzmann partition function and Simpson's rule for normalization, corresponding probability surfaces are generated which take account of the potential surface entropy. Comparing the two surfaces provides regions which are within a given probability contour of histamine but outside this contour for 4-methylhistamine. Thus, at the 99% probability level, three conformational regions defined by the bond rotation angles are indicated as possible "H1-essential" conformations of histamine: viz. trans (theta1=290-330 degrees, theta2=150-210 degrees) and gauche (theta1=260-280 degrees, theta2=30-90 degrees and theta1=290-320 degrees, theta2=270-320 degrees). This procedure provides a quantitative basis for comparison with other histamine derivatives and may have a general value for studying relationships between conformation and biological activity of closely related small molecules.

Energy Transfer↗