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M Westerfield

Publications and source records attributed to M Westerfield.

83 records · Page 5Linked to original sources

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↗

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↗

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↗

How Gymnodinium breve red tide toxin(s) produces repetitive firing in squid axons.

Partially purified toxin(s), GbTX, extracted from Gymnodinium breve red tide organisms elicits a spontaneous train of action potentials in the squid giant axon. The spikes have a shape similar to that in the normal seawater control except for an increase in the rate of recovery from the afterhyperpolarization. With this more rapid recovery, the membrane potential overshoots the resting potential and threshold, triggers another spike, and thus produces repetitive firing. Voltage-clamp studies revealed that the toxin has no effect on the normal sodium or potassium conductance changes produced by step depolarization. However, consistent with the faster recovery after an action potential, GbTX speeds recovery of the "shut-off" currents to their steady-state values after a depolarization. The most likely mechanism by which the toxin accelerates recovery after an action potential (leading to repetitive firing) is the induction of a small additional inward current which was found to be reduced by prehyperpolarization. This toxin-induced current which speeds recovery is blocked by tetrodotoxin and hence presumably flows through the sodium channel.

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↗

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↗

Pathway selection by growth cones of identified motoneurones in live zebra fish embryos.

How is the adult pattern of connections between motoneurones and the muscles that they innervate established during vertebrate development? Populations of motoneurones are thought to follow one of two patterns of development: (1) motor axons initially follow stereotyped pathways and project to appropriate regions of the developing muscle or (2) motor axons initially project to some regions that are incorrect, the inappropriate projections being eliminated subsequently. Here we observed individually identified motoneurones in live zebra fish embryos as they formed growth cones and as their growth cones navigated towards their targets. We report that from axogenesis, each motor axon followed a stereotyped pathway and projected only to the specific region of the muscle appropriate for its adult function. In addition, the peripheral arbor established by each motoneurone was restricted to a stereotyped region of its own segment and did not overlap with the peripheral arbor of the other motoneurones in that segment. We conclude that the highly stereotyped pattern of innervation seen in the adult is due to initial selection of the appropriate pathway, rather than elimination of incorrect projections.

Animals↗

Pathologic afflictions of the Achilles tendon.

The Achilles tendon represents a very important structure in human locomotion. Pathologic afflictions of this tendon may lead to serious problems if not recognized and treated appropriately. Drs. Reinherz, Granoff, and Westerfield briefly review normal tendon anatomy and function. The mechanisms of tendon injury with clinical recognition of pathology, both objective and subjective, are then discussed. Proper management of the compromised tendo Achillis is presented.

Achilles Tendon↗

Management of trauma to the fifth metatarsal bone.

The fifth metatarsal bone is a complex kinesiologic entity. It serves as the attachment of several soft tissue structures, and undergoes a distinctive range of motion. The lateral pedal location predisposes this bone to various reactive forces, and subsequent pathologic conditions. Anatomic and biomechanical review, with classification of fifth metatarsal injuries, and treatment recommendations, are discussed in the following manuscript.

Fracture Fixation, Internal↗