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Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001.

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Neuroscience. 2nd edition.

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Quantal Transmission at Neuromuscular Synapses

Much of the evidence leading to the present understanding of chemical synaptic transmission was obtained from experiments examining the release of acetylcholine at neuromuscular junctions. These synapses between spinal motor neurons and skeletal muscle cells are simple, large, and peripherally located, making them particularly amenable to experimental analysis. Such synapses occur at specializations called end plates because of the saucerlike appearance of the site on the muscle fiber where the presynaptic axon elaborates its terminals (Figure 5.4A). Most of the pioneering work on neuromuscular transmission was performed by Bernard Katz and his collaborators at University College London during the 1950s and 1960s, and Katz has been widely recognized for his remarkable contributions to understanding synaptic transmission. Though he worked primarily on the frog neuromuscular junction, numerous subsequent experiments have confirmed the applicability of data about events at this particular synapse to transmission at chemical synapses throughout the nervous system.

Figure 5.4. Synaptic transmission at the neuromuscular junction.

Figure 5.4

Synaptic transmission at the neuromuscular junction. (A) Experimental arrangement, typically using the muscle of a frog or rat. The axon of the motor neuron innervating the muscle fiber is stimulated with an extracellular electrode, while an intracellular (more...)

When an intracellular microelectrode is used to record the membrane potential of a muscle cell, an action potential in the presynaptic motor neuron can be seen to elicit a transient depolarization of the postsynaptic muscle fiber. This change in membrane potential, called an end plate potential (EPP), is normally large enough to bring the membrane potential of the muscle cell well above the threshold for producing a postsynaptic action potential (Figure 5.4B). The postsynaptic action potential triggered by the EPP causes the muscle fiber to contract.

One of Katz’s seminal findings, in studies carried out with Paul Fatt in 1951, was that spontaneous changes in muscle cell membrane potential occur even in the absence of stimulation of the presynaptic motor neuron (Figure 5.4C). These changes have the same shape as EPPs but are much smaller (typically less than 1 mV in amplitude, compared to an EPP of perhaps 40 or 50 mV). Both EPPs and these small, spontaneous events are sensitive to pharmacological agents that block postsynaptic acetylcholine receptors, such as curare (see Box A in Chapter 7). These and other parallels between EPPs and the spontaneously occurring depolarizations led Katz and his colleagues to call these spontaneous events miniature end plate potentials, or MEPPs.

The relationship between the full-blown end plate potential and MEPPs was clarified by careful analysis of the EPPs. The magnitude of the EPP provides a convenient electrical assay of neurotransmitter secretion from a motor neuron terminal; however, measuring it is complicated by the need to prevent muscle contraction from dislodging the microelectrode. The usual means of eliminating muscle contractions is either to lower Ca2+ concentration in the extracellular medium or to partially block the postsynaptic transmitter receptors with the drug curare. As expected from the scheme illustrated in Figure 5.3, lowering the Ca2+ concentration reduces neurotransmitter secretion, thus reducing the magnitude of the EPP below the threshold for postsynaptic action potential production and allowing it to be measured more precisely. Under such conditions, stimulation of the motor neuron produces very small EPPs that fluctuate in amplitude from trial to trial (Figure 5.4D). These fluctuations give considerable insight into the mechanisms responsible for neurotransmitter release. In particular, the evoked response in low Ca2+ is now known to result from the release of unit amounts of neurotransmitter by the presynaptic nerve terminal. Indeed, the amplitude of the smallest evoked response is strikingly similar to the size of single MEPPs (compare Figure 5.4C and D). Further supporting this similarity, increments in the EPP response (Figure 5.5A) occur in units about the size of single MEPPs (Figure 5.5B). These “quantal” fluctuations in the amplitude of EPPs indicated to Katz and colleagues that EPPs are made up of individual units, each equivalent to a MEPP.

Figure 5.5. Quantized distribution of EPP amplitudes evoked in a low Ca2+ solution.

Figure 5.5

Quantized distribution of EPP amplitudes evoked in a low Ca2+ solution. Peaks of EPP amplitudes (A) tend to occur in integer multiples of the mean amplitude of MEPPs, whose amplitude distribution is shown in (B). The leftmost bar in the EPP amplitude (more...)

The idea that EPPs represent the simultaneous release of many MEPP-like units can be tested statistically. A method of statistical analysis based on the independent occurrence of unitary events (called Poisson statistics) predicts what the distribution of EPP amplitudes would look like during a large number of trials of motor neuron stimulation, under the assumption that EPPs are built up from unitary events like MEPPs (see Figure 5.5A). The distribution of EPP amplitudes determined experimentally was found to be just that expected if transmitter release from the motor neuron is indeed quantal (the red curve in Figure 5.5A). Such analyses confirmed the idea that release of acetylcholine does indeed occur in discrete packets, each equivalent to a MEPP. In short, a presynaptic action potential causes a postsynaptic EPP because it synchronizes the release of many transmitter quanta.

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By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2001, Sinauer Associates, Inc.
Bookshelf ID: NBK11028

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