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Biomedical subjects

R W Joyner

Publications and source records attributed to R W Joyner.

At least 73 records · Page 4Linked to original sources

Purkinje and ventricular activation sequences of canine papillary muscle. Effects of quinidine and calcium on the Purkinje-ventricular conduction delay.

We have studied in vitro preparations of canine right and left papillary muscles to determine the excitation sequences of the Purkinje and ventricular cells, using both monopolar surface electrodes and intracellular microelectrodes. Our results show, for right papillary muscles, that the Purkinje layer covers the basal part of the muscle, and that activation from the right bundle branch propagates over all of the Purkinje layer, but directly activates the underlying ventricular layer only at specific junctional sites. Left papillary muscles have attachments to both apical and basal Purkinje strands and the Purkinje layer covers the entire muscle, but, as for right papillary muscles, activation from the Purkinje layer to the ventricular layer occurs only at basal junctional sites. Antidromic conduction in papillary muscles (propagation from the ventricular layer to the Purkinje layer) can occur at regions other than the specific sites through which the Purkinje layer activates the ventricular layer. At the identified junctional sites, the Purkinje cell action potential duration is significantly shorter than in the free-running strand, but it remains longer than that of the ventricular cells. The time delay at the junctional sites is increased by quinidine, increased calcium concentration, and increased pacing frequency.

Action Potentials↗

Propagation through electrically coupled cells. Effects of regional changes in membrane properties.

The normal process of excitation of the heart involves propagation of action potentials through cardiac regions of different anatomy and different intrinsic membrane properties. Although our understanding of these properties is still incomplete, it is well accepted that the parameters measured from a single cell penetration in an electrical syncytium (e.g., action potential duration, rate of rise, and velocity) reflect not only the properties of that cell but also the electrotonic interactions with other cells to which the recorded cell is electrically coupled. We have used simulation techniques to predict the spatial distribution of action potential parameters resulting from discretely localized alterations in the intrinsic membrane properties of some of the cells of an electrical syncytium. We have shown that the resulting spatial distribution is markedly different for alterations in plateau and pacemaker currents vs. rising phase currents, and that other factors, such as the site of stimulation and the underlying spatial pattern of cell-cell coupling resistance, also modify the spatial distribution of action potential properties resulting from a discrete regional change in intrinsic membrane properties.

Action Potentials↗

Postsynaptic factors controlling the shape of potentials at the squid giant synapse.

The roles of rectification and cable properties of the squid giant axon in determining the shape of synaptic potentials generated at the giant synapse were investigated. Excitatory postsynaptic potentials were recorded in response to selective stimulation of the main presynaptic axon at various temperatures. Excitatory postsynaptic potentials elicited at low temperatures (less than 18 degrees C) exhibited a marked after-hyperpolarization or undershoot, while those recorded at higher temperatures did not. The postsynaptic current, recorded under voltage clamp conditions, did not show an undershoot. Furthermore, intracellular injection of tetraethylammonium chloride, to block the voltage-dependent rise in potassium conductance, also eliminated the undershoot of the excitatory postsynaptic potential. These results indicate that the duration of synaptic potentials at the squid giant synapse is reduced by rectification due to a delayed rise in potassium conductance. Computer simulations of these synaptic potentials suggested that the effects of rectification will be more prominent in spherical (isopotential) cells than in cells with more complicated geometries.

Animals↗

Effects of rectification on synaptic efficacy.

We have investigated the effects of postsynaptic membrane properties on the shape of synaptic potentials generated by time-varying synaptic conductances. We used numerical simulation techniques to model cells of several different geometrical forms, from an isopotential sphere to a neuron with a soma and a dendritic tree. A variety of postsynaptic membrane properties were tested: (a) a passive resistance-capacitance membrane, (b) a membrane represented by the Hodgkin and Huxley (HH) equations, and (c) a membrane that was passive except for a delayed rectification represented by a voltage- and time-dependent increase in GK. In all cases we investigated the effects of these postsynaptic membrane properties on synaptic potentials produced by synaptic conductances that were fast or slow compared with the membrane time constant. In all cases the effects of postsynaptic rectification occurred on postsynaptic potentials of amplitudes as low as 1 mV. The HH model (compared with the passive model) produced an increased peak amplitude (from the increase in GNa) but a decreased half-width and a decreased time integral (from the increase in GK). These effects of the HH GK change were duplicated by a simple analytical rectifier model.

Animals↗

Effects of the discrete pattern of electrical coupling on propagation through an electrical syncytium.

We used numerical integration techniques to simulate action potential propagation along one-dimensional strands of cells coupled with electrical junctions. We considered the standard case to be a series of cardiac cells (20 micrometer in diameter, 50 micrometers long) with intercellular coupling such that the effective longitudinal resistance was 200 omega cm. The membrane properties were represented by the model of Beeler and Reuter (1977) (Sharp and Joyner, 1980). By increasing Ri (and thus decreasing the space constant, L), we showed that effects due to the discrete cell length, delta X, became apparent when delta X/L was greater than about 0.2, producing an increased maximal dV/dt but a decrease in peak inward current. We also simulated the effects of a periodic spatial variation in Ri, representing a structure with groups of well-coupled cells but with minimal coupling between the groups. Even with a constant membrane model and cell size, variations in the spatial pattern of interconnection produced significant changes in action potential shape and velocity, with some patterns producing decremental conduction or propagation failure.

Action Potentials↗

Mechanisms of unidirectional block in cardiac tissues.

We used numerical solutions for cable equations representing nonuniform cardiac strands to investigate possible mechanisms of unidirectional block (UB) of action potential propagation. Because the presence of UB implies spatial asymmetry in some property along the strand, we varied membrane properties (gNa or leakage conductance), cell diameter, or intercellular resistance as functions of distance such that a propagating action potential encountered the parameter changes either gradually or abruptly. For changes in membrane properties there was very little difference in the effects on propagation for the gradual or abrupt encounter; but, for changes in cell diameter or in intercellular resistance, there were large differences leading to the production of UB over a wide range of parameter values.

Action Potentials↗

Temperature effects on neuronal elements.

This paper presents a review of the experimentally determined values for the temperature dependence of parameters of initiation and propagation of action potentials. These experimentally determined Q10 values are compared to the theoretical Q10 values predicted by the Hodgkin-Huxley (H-H) equations. The H-H equations (with a Q10 of 3 for the rate constants) accurately predict the temperature dependence of most of the measured parameters. In addition, it is shown that the H-H equations accurately predict the temperature dependence of propagational failure at regions such as branch points, where the safety factor can be lowered by geometric factors that produce an increased electrical load.

Action Potentials↗

Neuronal mechanisms for bilateral coordination of salivary gland activity in Helisoma.

The salivary neuroeffector system of Helisoma consists of the paired salivary glands and buccal ganglia. Previous work demonstrated that neuronal control was required for coordination of activity in the two salivary glands. This neuronal control is provided by a pair of identified buccal ganglion neurons, 4R and 4L. This study examines the organization of this neuronal control and addresses the questions of monosynaptic vs. polysynaptic pathways as well as the bilateral effects of each neuron 4. Action potentials in neuron 4 elicit one-for-one EPSPs in a subpopulation of the salivary cells. These EPSPs can, in some cases, be increased by TEA injection into a neuron 4 and are unaffected by the addition of six-times normal calcium. These data coupled with the constancy of synaptic transmission, as well as morphological evidence, further indicate the monosynaptic nature of the connection between neurons 4 and salivary secretory cells. Three different mechanisms exist to insure that activity in 4R and 4L result in coordinated activation of the salivary glands: (1) Lucifer Yellow injection and direct intracellular recording and stimulation demonstrate that both 4R and 4L can send axons to and innervate both salivary glands; (2) both 4R and 4L receive virtually identical synaptic input from higher-order buccal ganglion neurons; and (3) 4R and 4L are electrically coupled. Thus, the system is organized with a high degree of redundancy, and bilateral synchrony of glandular activity is assured by mechanisms at various levels of neuronal organization.

Action Potentials↗

Effects of cellular geometry on current flow during a propagated action potential.

An impulse propagating in a cell with nonuniform geometry sees an increased electrical load at regions of increasing diameter or at branch points with certain morphologies. We present here theoretical and experimental studies on the changes in membrane current and axial current associated with diameter changes. The theoretical studies were done with numerical solutions for cable equations that were generalized to include a varying diameter; the Hodgkin-Huxley equations were used to represent the membrane properties. The experimental studied were done using squid axons with the axial insertion of platinized platinum wires to create a localized region of increased electrical load. As an action potential approaches a region of increased electrical load, the action potential amplitude and rate of rise decrease, but there is a marked increase in the magnitude of the inward sodium current. The time integrals of the inward and outward currents are not constant along the fiber and indicate net inward charge movement at regions subjected to an increased electrical load. Changes in the waveform of the axial current at such a region help to explain the temperature dependence of propagation failure at regions of increasing electrical load.

Action Potentials↗

Simulated propagation of cardiac action potentials.

We have used numerical methods for solving cable equations, combined with previously published mathematical models for the membrane properties of ventricular and Purkinje cells, to simulate the propagation of cardiac action potentials along a unidimensional strand. Two types of inhomogeneities have been simulated and the results compared with experimentally observed disturbances in cardiac action potential propagation. Changes in the membrane model for regions of the strand were introduced to simulate regions of decreased excitability. Regional changes in the intercellular coupling were also studied. The results illustrate and help to explain the disturbances in propagation which have been reported to occur at regions of decreased excitability, regions with changing action potential duration, or regions with changing intercellular coupling. The propagational disturbances seen at all of these regions are discussed in terms of the changing electrical load imposed upon the propagating impulse.

Action Potentials↗

A numerical method to model excitable cells.

We have extended a fast, stable, and accurate method for the numerical solution of cable equations to include changes in geometry and membrane properties in order to model a single excitable cell realistically. In addition, by including the provision that the radius may be a function of distance along an axis, we have achieved a general and powerful method for simulating a cell with any number of branched processes, any or all of which may be nonuniform in diameter, and with no restriction on the branching pattern.

Action Potentials↗

Simulations of conduction in uniform myelinated fibers. Relative sensitivity to changes in nodal and internodal parameters.

Conduction of impulses in myelinated axons has been studied by a new method of computer simulation. The contributions of nodal and internodal characteristics and parameters were examined. Surprisingly, the conduction velocity, theta, was found to be quite insensitive to the nodal area or the exact description of its excitable processes. The conduction velocity also is relatively insensitive to the internodal length but much more sensitive to the myelin capacitance and axoplasm conductance. Qualitative change in theta with temperature depended on which temperature-sensitive parameters were included in the simulation.

Axons↗

Temperature-sensitive conduction failure at axon branch points.

1. The propagation of action potentials through the branching regions of squid axons was examined experimentally and with computer simulations over a temperature range of 5-25 degrees C. 2. Above a critical ratio of postbranch to prebranch diameters, propagation of an action potential failed. The value of this critical ratio is very sensitive to temperature and is smaller at high temperatures. The experimentally measured Q10 of the critical ratio is 0.37 +/- 0.04. 3. Evaluation of a number of parameters of action-potential propagation showed that this effect is closely related to the change in the width of the action potential with temperature (Q10 = 0.29 +/- 0.01).

Action Potentials↗

Conduction velocity and spike configuration in myelinated fibres: computed dependence on internode distance.

It has been argued theoretically and confirmed experimentally that conduction velocity (theta) should be proportional to nerve fibre diameter for myelinated fibre tracts, such as normal peripheral nerve, exhibiting 'structural' similarity'. In some axons, however, the nodes of Ranvier are more closely spaced than in normal peripheral nerve. Analytic arguments have suggested that when internodal distance (L) alone is changed, the plot of theta versus L should have a relatively flat maximum. This was confirmed by several previous computer simulations of myelinated axons, but internode lengths of less than half the normal case were not examined. In order to gain insight into impulse propagation in myelinated and remyelinated fibres with short internodal lengths, the present study examines the conduction velocity and spike configuration for a wide range of internodal lengths. As L becomes large, theta falls and finally propagation is blocked; as L becomes small, theta decreases more and more steeply. From this, it is predicted that for fibres with very short internodal lengths, small local changes in L should affect substantially the conduction velocity.

Action Potentials↗

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↗

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↗