Biomedical subjects
N Stockbridge
Publications and source records attributed to N Stockbridge.
Dynamics of intracellular calcium and its possible relationship to phasic transmitter release and facilitation at the frog neuromuscular junction.
We have developed a mechanistic model for intracellular influx, diffusion, and efflux of calcium, and we compare its predictions to the dynamics of transmitter release at the frog's motor nerve terminal. The model includes a square wave influx of calcium, a linear or saturable pump for the efflux of calcium, and slow diffusion of calcium within the terminal due to rapid equilibrium binding of the major portion of the influx to fixed, nonsaturable sites in the cytoplasm. Transmitter release is taken as proportional to the fourth power of the calcium concentration in a region within 100 A of the surface membrane. The model predicts phasic release of transmitter with a time course similar to that of the endplate current--it turns on with a lag, rises rapidly to a peak, and then declines more slowly. It also predicts facilitation, the increased transmitter release in response to a second stimulus for many milliseconds after the initial transmitter release has ceased. This facilitation is similar to that reported at the frog neuromuscular junction in its initial amplitude and time course.
On the site of impulse initiation in a neurone.
In the preceding paper (Moore & Westerfield, 1983) the effects of changes in membrane properties and non-uniform geometry on impulse propagation and threshold parameters were investigated. In this paper the contributions of these and other parameters to the site of initiation of an impulse were determined by computer simulations using the Hodgkin-Huxley membrane description, the cable equations, and geometry appropriate for a simplified motoneurone with a non-myelinated axon. Antidromic invasion of action potentials into the soma was found to depend upon (a) the ionic channel rate constants (determined by the temperature), (b) the abruptness of the transition from the small-diameter axon to the larger diameter (and increased load) of the soma-dendrite, (c) extensions of active properties into the dendrite, and (d) density of ion channels. The location of the apparent site of initiation of impulses was not necessarily at the site of synaptic input nor the nearest active membrane. Its position depended upon (a) the fraction of the dendritic tree with excitable membrane, and secondarily on (b) the stimulus strength. Even with uniform excitability in the active membrane, the apparent site of initiation could be moved a considerable distance from the soma and the site of stimulation by appropriate choice of the various parameters noted above.
Presynaptic calcium diffusion and the time courses of transmitter release and synaptic facilitation at the squid giant synapse.
At the squid giant synapse, a presynaptic action potential is accompanied by an influx of calcium ions that continue to be detectable with arsenazo III microspectrophotometry for several seconds. Nevertheless, transmitter release occurs phasically, lasting only about 2 msec. If a second action potential follows within about 100 msec after the first, it releases more transmitter. In this paper, we present a mathematical model of intracellular calcium diffusion with binding to fixed cytoplasmic sites, active extrusion at the surface, and influx during an action potential, to predict the distribution of intracellular calcium following an action potential. With a square law relation between submembrane calcium and transmitter release, the model predicts the phasic release of transmitter and the magnitude and time course of synaptic facilitation following an action potential, as well as the relatively long persistence of free intracellular calcium.
A re-examination of the residual calcium theory for facilitation of transmitter release.
Explore the source record for details and available documents.
On the squid axon membrane's response to sequential voltage and current clamps.
Starzak and Starzak (1978. IEEE Trans. Biomed. Eng. 25:201-204.) proposed that, in cyclic application of current and voltage-clamps, the fidelity of the match of the output current with the original stimulus could be used to measure the spatial uniformity of voltage in a membrane. However, they failed to find such a match in experiments on either squid axons or an electronic model of a membrane patch. Computer simulations of such experiments show that the failure to return the initial pattern may arise from shortcomings of the instruments or instability of membrane characteristics. Logical arguments show that such cyclic experiments are not able to provide information about spatial gradients of membrane voltage.
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.
Localized Ca2+ and calcium-activated potassium conductances in terminals of a barnacle photoreceptor.
Calcium channels are found in the presynaptic terminals of neurones, where they have a key role in synaptic transmission. They are also found in the somata of many cells, in dendrites and along a few axons. In no cell is the actual distribution of these channels known in detail, because there are no known toxins or other agents suitable for labelling calcium channels, and the current through these channels is usually too small to be quantified with extracellular electrodes. However, several experiments have suggested that the density of the channels is less in the axon than in the cell body or terminal region. Here we have used the indicator dye Arsenazo III in conjunction with an array of photodetectors to examine the spatial influx of calcium in the presynaptic terminal region of the giant barnacle, Balanus nubilus. In these cells, calcium entry occurs in a restricted region less than 50 micron in length, which corresponds closely to the region of synaptic contact with second-order cells. Outside this area the magnitude of calcium entry is reduced at least 50-fold. With reasonable assumptions it follows that the calcium channel density is equally localized. In addition, we demonstrate that these cells have a calcium-activated potassium conductance. Since calcium entry is restricted to the synaptic zone, this conductance must be effective only in this region.