Neuroscience
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Cellular and Molecular Neurobiology
5. Mechanisms of Neurotransmitter Release
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Neuroscience
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Cellular and Molecular Neurobiology
5. Mechanisms of Neurotransmitter Release
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Figure 5.1 |
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Just before the presynaptic axon was stimulated a second time, the switch was briefly closed to eject a small amount of calcium in the vicinity of the presynaptic terminal. A normal EPSP was recorded. The experiment was repeated a third time, but now the calcium ejection occurred after the presynaptic axon was stimulated. There was no EPSP. This experiment demonstrates that calcium must be present before or during the action potential in the presynaptic terminal. Based on this experiment and others like it, Katz and colleagues proposed the calcium hypothesis for chemical synaptic transmission.
| How does the increase in the intracellular concentration
of Ca2+ cause transmitter release? The answer to this question
came from an experiment which initially seems unrelated to the issue. Using
high amplification of the electrical recording system, Katz noticed small
deflections that occurred spontaneously and randomly at a rate of about
once every 50 msec (Panel A of the figure to the right).
These small deflections had interesting properties.
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Figure 5.3 |
(The designation MEPP has a very specific meaning. It refers to those small endplate potentials that occur randomly in the absence of any stimulation. For example, small endplate potentials (EPPs) can be recorded in the presence of curare or low levels of extracellular Ca2+ , but they are not MEPPs.)
Katz suggested, as a result of the experiment illustrated in Figure 5.3, that the normal EPP is due to the summation effects of many vesicles being released at the same time. One vesicle produces a potential of about 0.5 mV. The release of 100 of those vesicles at the same time could produce a potential which is 100 times as great (50 mV).
The illustration below (Figure 5.4) shows one of these vesicles in the process
of fusing with the membrane and releasing its contents into the synaptic cleft
through a process called exocytosis. For
illustrative purposes, each synaptic vesicle is shown to contain three molecules
of transmitter. In reality, each vesicle contains about 10,000 molecules of
transmitter. Vesicles ready to be released are found in a region near the presynaptic
terminal membrane called the releaseable pool.
Newly synthesized vesicles are found in the storage
pool. The process by which a vesicle migrates from the storage pool to the
releaseable pool is called mobilization. After
fusing with the membrane and releasing its contents, the membrane is recycled
to form new synaptic vesicles. This process is called recycling.
Additional details of this process are found in Chapter
10.
| Figure 5.4 |
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Figure 5.5 |
An experiment by Katz that further supported the quantal hypothesis for chemical synaptic transmission is shown above. The extracellular concentration of calcium was lowered to reduce the size of the evoked endplate potential. Because less Ca2+ is in the extracellular medium, less Ca2+ will be available to enter through the voltage-dependent Ca2+ channels. At the arrow, the electrical shock was delivered to the motor axon. Eight successive stimuli were delivered to the presynaptic terminal. EPSPs with stars are the miniature endplate potentials (MEPPs). Note that they are uncorrelated with the stimulus. The evoked endplate potentials are small and highly variable. Sometimes the EPP was 1.6 mV in amplitude; sometimes there was no EPP at all. Sometimes the EPP was 0.4 mV. Katz noticed that these amplitudes showed a specific kind of distribution. The smallest evoked responses were 0.4 mV. He called these responses "units". Other times he recorded EPPs that were about 0.8 mV and called such responses "doubles" because they were twice the unit, and sometimes responses were 1.6 mV. Figure 5.5 is a plot of the number of times an EPP of various amplitudes was observed. Katz noticed that the amplitude of the smallest EPP that could be evoked was the same amplitude (0.5 mV) as the amplitude of the MEPP.
Based on these results Katz proposed the quantal hypothesis for chemical synaptic transmission. An action potential in the presynaptic cell produces an influx of Ca2+ which promotes the exocytosis of synaptic vesicles from the presynaptic terminal. There is a statistical variability in the amount of vesicles that can be released. When the extracellular calcium concentration is low, sometimes there is not enough calcium to release any vesicles. At other times, there is enough calcium to cause the release of one vesicle and other times two vesicles, or three vesicles, and so forth. Each peak is therefore an integral multiple of the next, indicating that these vesicles are released in a quantized fashion. With normal levels of calcium, there is sufficient influx of Ca2+ to release about 100 vesicles, which produce an endplate potential (EPP) of about 50 mV.
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Figure 5.6 Place cursor over graphic to see labels. |
Figure 5.6, above, illustrates a summary of the steps involved in the process of synaptic transmission at the neuromuscular junction.
Test Your Knowledge |
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5. In a normal, healthy individual the number of ACh-sensitive channels in a skeletal muscle cell opened as a result of a single action potential in a motor axon would be approximately. |
| 6. An isolated nerve muscle preparation treated with a moderate dose of curare would be associated with a decrease in the (Note: There is more than one correct answer.) |
| 7. An isolated nerve muscle preparation exposed to a low concentration of extracellular Ca2+ would be associated with a decrease in the (Note: There is more than one correct answer.) |
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Contact the author(s) at: nba_course@uth.tmc.edu
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The University of Texas Health Science Center at Houston
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