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J Holsapple

Publications and source records attributed to J Holsapple.

4 recordsLinked to original sources

Further evidence for the dynamic formation of transmitter quanta at the neuromuscular junction.

Fatt and Katz (Nature 166:597-598, 1950; J Physiol 117:109-128, 1952) attributed miniature endplate potentials (MEPPs) to the action of a standard quantity of transmitter, the quantum (Del Castillo and Katz, J Physiol 124:560-573, 1954). Quantal packets of transmitter were proposed to be preformed (Del Castillo and Katz, In CNRS Paris (Ed): "Microphysiologie comparée des éléments excitables" 67:245-258, 1957) and stored in large numbers in the motor nerve terminal. Statistical analyses of intervals between MEPPs and numbers of quanta composing small endplate potentials indicated that quantal release was a random process and that release sites functioned independently of each other. With the discovery of synaptic vesicles it was proposed that each contained one quantum of transmitter. The quantal-vesicular hypothesis (Del Castillo and Katz, as cited above) fails, however, to explain amplitude distributions of MEPPs that are skewed and/or that show multiple peaks (Kriebel et al., Brain Res Review 15:167-178, 1990). The drop formation process (Shaw, "The Dripping Faucet as a Model Chaotic System," Santa Cruz, CA: Aerial Press, Inc., 1984) was shown to generate amplitude classes of drops that were similar to classes of MEPPs which suggested that rapid changes in quantal size and ratios of skew- to bell-MEPPs could be explained with a simple dynamic process which determines quantal size at the moment of release (Kriebel et al., as cited above, 1990). Further similarities between miniature endplate currents (MEPCs) and the formation of drops are reported here. We found that rapid changes in MEPC amplitudes and time courses, which accompany an increase in frequency, mimic changes in drop sizes that accompany increases in flow rate. MEPC intervals have a minimum and their distributions are comparable to those of drop intervals. During an increased rate of transmitter release, MEPP amplitudes and intervals were positively correlated. The results suggest that spontaneously released transmitter "packets" are formed at the moment of release and that transmitter supply to the process that forms packets is continuous.

Animals↗

Effects of DFP on unit activity in rat superior colliculus.

The effect of systemically administered diisopropylfluorophosphate (DFP) on the spontaneous firing rate and light-evoked responses of rat superior colliculus neurons was determined from average histograms of single unit and multiunit activity. DFP produced a dose-dependent increase in superior colliculus spontaneous activity, and a decrease in light evoked activity. In many experiments, light evoked responses were completely abolished. The changes in spontaneous activity were reversible over a period of about 5 hours following DFP injection. These results establish the retino-tectal pathway as a major target of DFP toxicity.

Action Potentials↗

Transmitter release: prepackaging and random mechanism or dynamic and deterministic process.

Stepwise variations in end-plate potential amplitudes that are also multiples of spontaneous miniature end-plate potentials (MEPPs) demonstrate a quantal nature of evoked transmitter release at the vertebrate neuromuscular junction. Both the number of quanta which form relatively small end-plate potentials (EPPs) and the time intervals between MEPPs were found to fit Poisson statistics. These observations suggested that the release process randomly liberates uniform quantities of transmitter. Initial studies showed that quantal size remained stable after seemingly high rates of release which was interpreted to indicate that a large store of equally sized, equally available, and independently releasable quanta are present in the nerve terminals. The observation of numerous presynaptic vesicles that contain transmitter provided a morphological basis for prepacked transmitter (i.e., quanta). However, physiological studies over the last 15 years have yielded data that are difficult to incorporate into the quantum-vesicle hypothesis. With normal conditions and during most treatments which increase the rate of release, two classes of MEPPs have been found and both show a substructure. The bell-MEPP class was characterized by Fatt and Katz and the smaller skew-MEPP class has been studied by Kriebel. The ratio of the two classes and substructure compositions of both classes are variable. Short series of MEPPs and unitary EPPs (U-EPPs) show preferred amplitudes and longer series of MEPPs and U-EPPs show stepwise variations in amplitude. Slow-MEPPs and giant MEPPs belong to the skew class and represent nearly synchronous bursts of smaller MEPPs. Transmitter packet formation, preferred amplitudes, stepwise variations in amplitudes, random-like distributions and organized bursts can be simulated by a simple deterministic system, the drop formation process, that is known for its periodic and chaotic behaviors which are determined by the single parameter of flow rate. MEPP intervals, sizes and classes, are also dependent on rates of release which demonstrate that the release process(es) is highly organized and sensitive to different conditions. We demonstrate that the processes of drop formation and release of a packet of transmitter have similar properties and that deterministic characteristics describe MEPP and U-EPP time dependencies and amplitude substructures. The data and model presented here suggest that packet size of acetylcholine may be determined at the moment of release.

Animals↗