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Biomedical subjects

J W Moore

Publications and source records attributed to J W Moore.

At least 235 records · Page 13Linked to original sources

A kinetic model for the sodium conductance system in squid axon.

We describe a kinetic reaction sequence for the sodium conductance system in the squid axon. It closely matches the original Hodgkin and Huxley model for voltage clamp experiments but it generates an action potential without a bump on the falling phase. When calcium ions are included in the reaction, this model faithfully reproduces the experimental observations of Frankenhaeuser and Hodgkin on the effects of altered calcium in the medium. The fit to experiment is much better than when a voltage shift in rate constants is assumed. The gating currents recently observed by Armstrong and Bezanilla are not compatible with the Hodgkin and Huxley model but can be reprocuced in considerable detail by the kinetic model. Thus it appears that the kinetic model differs from that of Hodgkin and Huxley perhaps in an important and fundamental way that makes it more realistic.

Animals↗

Squid giant axons. A model for the neuron soma?

Insertion of electrically floating wires along the axis of a squid giant axon produces an apparent increase in diameter in the region where the wire surface has been treated to give it a low resistance. The shape of action potentials propagating into this region depend upon the surface resistance (and the length) of the wire. As this segment's internal resistance is lowered by reducing the wire's surface resistance, the following characteristic sequence of changes in the action potential is seen at the transition region: (a) the duration increases; (b) two peaks develop, the first one generated in the normal axon region and the second one generated later in the axial wire region, and; (c) blockage occurs (for a very low resistance wire). Action potentials recorded at the membrane region near the tip of the axial wire in (b) resemble those recorded at the initial segment of neurons upon antidromic invasions. Squid axon action potentials propagated from a normal region into that containing the low resistance wire also resemble antidromic invasions recorded in neuron somas. Hyperpolarizing current pulses applied through the wire act as if the wire surface resistance was momentarily reduced. For example, the two components of the action potential recorded at the axial wire membrane region noted in (b) can be sequentially blocked by the application of increasing hyperpolarizing current through the wire. Similar effects are seen when hyperpolarizing currents are injected into motoneuron somas. It is concluded that the geometrical properties of the junction of a neuron axon with its soma may be in themselves sufficient to determine the shape of the action potentials usually recorded by microelectrodes.

Action Potentials↗

An octopus toxin, maculotoxin, selectively blocks sodium current in squid axons.

1. A low molecular weight, stable, cationic neurotoxin (maculotoxin, MTX) extracted from the posterior salivary glands of the octopus Hapalochlaena maculosa, blocked sodium current in voltage-clamped squid axons without affecting potassium current. 2. The effectiveness of MTX was increased by repetitive, brief, depolarizing pulses but not by a single prolonged depolarization. 3. The potency of MTX decreased at pHs from 8 to 9. Effectiveness could be restored be restored by lowering the pH to 7-1 again. It was concluded that MTX is active in its cationic form. 4. MTX affected sodium conductance kinetics, slowing the turn-on of sodium current. This effect was most noticeable with small deploarizations but became progressively less with larger depolarizations. Neither the turn-off of sodium current nor sodium inactivation kinetics were affected by the toxin. 5. MTX inhibited sodium current without inhibiting sodium gating current. 6. The effectiveness of MTX was not detectably changed when calcium concentration was varied from 50 to 10 mM, or sodium concentration was varied from 225 to 750 mM.

Animals↗

A job rating scale for use in psychiatric rehabilitation.

Work has been a highly valued feature of psychiatric rehabilitation programmes. The performance of patients has often been the object of scrutiny and assessment, but the jobs performed by these patients have not been so assessed. This paper describes the development and use of a job rating scale which parallels the use of patient assessment instruments.

Achievement↗

Variation of the sella-nasion plane and its effect on SNA and SNB.

The sella-nasion plane is one of the basic planes used in the cephalometric evaluation of candidates for orthognathic surgery. The relationship between SN and the Frankfort horizontal plane was studied. It was shown that as the angle between FH and SN increases, the SNA and SNB angles decrease in the normal individual. Compensation can be made for this variation by using the values presented.

Cephalometry↗

Mechanical performance of surgical sutures.

A comprehensive analysis of the mechanical performance of sutures has been made to provide information concerning the reliability and security of knotted sutures. The tests utilized in this analysis were designed to be easily reproduced by other investigators. The construction of the knot and the knot performance analysis were undertaken utilizing an Instron Tensile Tester. The mechanical reliability of each knotted suture was determined by measuring the number of throws to reach knot break, the expected slippage of the knot when it reaches knot break, and the maximal holding force at knot break. On the basis of these measurements, recommendations are made for the use of a suture at operation.

Biomechanical Phenomena↗

Axon voltage-clamp simulations. I. Methods and tests.

This is the first in a series of four papers in which we present the numerical simulation of the application of the voltage clamp technique to excitable cells. In this paper we describe the application of the Crank-Nicolson (1947) method for the solution of the parabolic partial differential equations that describe a cylindrical cell in which the ionic conductances are functions of voltage and time (Hodgkin and Huxley, 1952). This method is compared with other methods in terms of accuracy and speed of solution for a propagated action potential. In addition, differential equations representing a simple voltage-clamp electronic circuit are presented. Using the voltage clamp circuit equations, we simulate the voltage clamp of a single isopotential membrane patch and show how the parameters of the circuit affect the transient response of the patch to a step change in the control potential. The stimulation methods presented in this series of papers allow the evaluation of voltage clamp control of an excitable cell or a syncytium of excitable cells. To the extent that membrane parameters and geometrical factors can be determined, the methods presented here provide solutions for the voltage profile as a function of time.

Action Potentials↗

Axon voltage-clamp simulations. II. Double sucrose-gap method.

This is the second in a series of four papers on the simulation of the voltage clamp of cylindrical excitable cells. In this paper we evaluate the double sucrose-gap voltage-clamp technique for the squid and lobster giant axons. Using the Crank-Nicolson method of solution of the cable equations and differential equations representing the voltage clamp circuit we studied the effect of length of the sucrose gap "node" on the voltage profile along an excitable cell during a simulated voltage clamp. The voltage gradients along the region of the cell within the node produce "notches" in the current recording as well as changes in the magnitude of the sodium and potassium current for a given voltage step. Our results show that good voltage clamp control requires node lengths less than one-half the axon diameter.

Action Potentials↗

Axon voltage-clamp simulations. III. Postsynaptic region.

This is the third in a series of four papers in which we present the numerical simulations of the application of the voltage clamp technique to excitable cells. In this paper we discuss the problem of voltage clamping a region of a cylindrical cell using microelectrodes for current injection and voltage recording. A recently developed technique (Llinás et al., 1974) of internal application of oil drops to electrically insulate a short length of the postsynaptic region of the squid giant synapse is evaluated by simulation of the voltage clamp of an excitable cylindrical cell of finite length with variable placement of the current and voltage electrodes. Our results show that ENa can be determined quite accurately with feasible oil gap lengths but that the determination of the reversal potential for the synaptic conductance, ES, can be considerably in error. The error in the determination of ES dependp, and especially the membrane resistance at the time the synaptic conductance occurs. It is shown that the application of tetraethylammonium chloride to block the active potassium conductance very significantly reduces the error in the determination of ES. In addition we discuss the effects of cable length and electrode position on the apparent amplitude and time course of the syn aptic conductance change. These results are particularly relevant to the application of the voltage clamp technique to cells with nonsomatic synapses. The method of simulation presented here provides a tool for evaluation of voltage clamp analysis of synaptic transmission for any cell with known membrane parameters and geometry.

Action Potentials↗

Axon voltage-clamp simulations. A multicellular preparation.

In this paper we extend the simulation of the voltage clamp of a single nerve fiber to a bundle of axons. These simulations included not only the description of the voltage clamp circuit and a single unidimensional cable to represent the preparation in the "node" region of a double sucrose gap used previously but also a series resistance and a shunt pathway. The output of the voltage control amplifier is applied across the membrane plus the series resistance, producing a voltage drop across the series resistance due to the current generated by the membrane in response to a depolarizing voltage step. Since the membrane current has an inward and an outward phase, voltage drops of opposite sign are produced across the series resistance. During the transient current and at all points along an axon, the potential deviation produced by the series resistance is opposite to the deviation produced by the longitudinal gradient. Only at a command potential equal to the sodium equilibrium potential, the membrane potential transiently matches the command potential. For the attempted voltage clamp of an axon, values of series resistance larger than 50 omega-cm2 allowed propagated action potentials in the membrane. In spite of the presence of propagated action potentials at the calbe membrane, the recorded current does not show "notches" and it has a phase of inward current and a phase of outward current. It is concluded that, in a multicellular preparation with series resistance, the recording of a square voltage pulse does not indicate voltage control of the transmembrane potential. The presence of a shunt pathway produces inaccurate values of current density. Neither series or shunt resistance produce "notches" in the current records.

Action Potentials↗

Classical differential and operant conditioning in rabbits (Oryctolagus cuniculus) with septal lesions.

Normal rabbits and rabbits with septal lesions received classical differential conditioning of the nictitating membrane response (NMR), followed by auditory generalization tests run in extinction. Although rate of acquisition and asymptotic responding to positive conditioned stimuli did not differ, septals responded more than normals to nonreinforced stimuli. Resultant decrements in differential conditioning could not be attributed to changes in auditory or shock thresholds or to increased spontaneous NMRs. Septals also responded at higher rates in both operant conditioning (bar presses reinforced with food pellets on a variable interval schedule) and extinction sessions. No difference in suppression in a passive avoidance task was found. Results are discussed in relation to McCleary's response disinhibition analysis of septal function, and an habituation hypothesis is considered.

Acoustic Stimulation↗

Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablation.

Rabbits received 0 to 450 exposures of a tone conditioned stimulus (CS) prior to classical defensive conditioning of the nicitating membrane response based on an infraorbital eye shock unconditioned stimulus. Tone preexposure resulted in retarded conditioning in normal rabbits. This latent inhibition effect was not present in animals with bilateral dorsal hippocampectomy produced by aspiration. Control animals with bilateral neocortical and callosal aspiration lesions demonstrated a latent inhibition effect similar to that shown by normal nonoperated animals. The failure of CS preexposure to retard conditioning in hippocampal rabbits was not due to differences in threshold of the conditioned response to the CS or to differences in response mechanisms as determined by tests of habituation and dishabituation of the unconditioned response. A subsequent experiment employed combined-cue summation tests to confirm the fact that preexposure did not endow the tone with conditioned as well as latent inhibitiory properties. Finally, tests of stimulus generalization along the auditory frequency dimension indicated flatter relative gradients for hippocampals than for nonoperated controls, with cortical controls in between. These findings were discussed in terms of Douglas' model of hippocampal function.

Acoustic Stimulation↗

The effect of signal probability, food intake, sex, and smoking on gustation, as measured by the theory of signal detection.

The possibility of applying Signal Detection Theory (SDT) to gustation was investigated by testing the effect of three variables--smoking, signal probability, and food intake (confounded with time of day)--on the taste sensitivity to sucrose of 24 male and 24 female Ss. No main effects or interactions were significant. The study indicated a "warm-up" effect, while adaptation was questionable. An analysis of false alarm (FA) reports was undertaken and discussed. Correlations were obtained between numerous variables and sensitivity. None of the correlations was statistically significant. It was concluded that although SDT is theoretically applicable to the gustatory modality, it is not practical for large-scale research.

Differential Threshold↗