what events in the presynaptic neuron lead to release of neurotransmitters
Chapter five: Mechanisms of Neurotransmitter Release
5.1 Function of Calcium in Transmitter Release
Calcium is a primal ion involved in the release of chemical transmitter substances. Bernard Katz and his colleagues examined its role using the skeletal nerve muscle synapse. Electrodes were placed near the presynaptic terminal to initiate an action potential in the last (Figure v.1). The preparation was perfused with a solution free of calcium. In guild to precisely control the delivery of calcium, some other microelectrode was filled with calcium. Since Catwo+ is positively charged, information technology can be delivered to the vicinity of the synaptic terminal past briefly endmost a switch connected to a battery in such a way that the positive pole forces infinitesimal amounts of calcium out of the electrode. In the absence of Ca2+ ejection, stimulation of the motor neuron produced no EPSP.
Only before the presynaptic axon was stimulated a 2nd time, the switch was briefly closed to squirt a pocket-sized amount of calcium in the vicinity of the presynaptic final. A normal EPSP was recorded. The experiment was repeated a 3rd time, but now the calcium ejection occurred subsequently the presynaptic axon was stimulated. There was no EPSP. This experiment demonstrates that calcium must be nowadays before or during the action potential in the presynaptic terminal. Based on this experiment and others like information technology, Katz and colleagues proposed the calcium hypothesis for chemical synaptic transmission.
The figure above illustrates some of the cardinal features of the calcium hypothesis for chemical synaptic transmission at the neuromuscular junction, but this hypothesis is by and large applicable to all chemic synapses in the nervous arrangement. There are ii parts to this hypothesis. Starting time, the depolarization of the presynaptic concluding leads to an increase in Ca2+ permeability. Just as there are voltage-dependent Na+ and G+ channels, at that place are likewise voltage-dependent Ca2+ channels. The structure of the voltage-dependent channels is very similar to the structure of the voltage-dependent sodium channels. Indeed, just a few amino acids can make the difference between a channel being selectively permeable to calcium and one that is selectively permeable to sodium. The Catwo+ channel is normally airtight, merely if there is a depolarization of the membrane (acquired by a presynaptic activity potential), the aqueduct opens and the opening of the aqueduct allows calcium influx. The second part of the calcium hypothesis for chemical synaptic transmission involves the consequences of the Ca2+ influx. The opening of the Caii+ channel allows for calcium to flow downward its concentration gradient from the outside to the inside of the synaptic concluding. This influx leads to an increase in the concentration of the Catwo+ in the presynaptic terminal, which past interacting with proteins associated with synaptic vesicles leads to the release of the chemical transmitter substance.
5.2 Calcium Hypotheses for Chemical Synaptic Transmission
Quantal Nature of Transmitter Release
How does the increase in the intracellular concentration of Caii+ cause transmitter release? The answer to this question came from an experiment which initially seems unrelated to the issue. Using high distension of the electric recording system, Katz noticed small deflections that occurred spontaneously and randomly at a rate of almost once every 50 msec (Panel A of the figure to the right).
These modest deflections had interesting properties.
- First, they occurred in the absenteeism of any stimulus.
- Second, they were minor with an average amplitude of nearly 0.5 mV. The distribution could be fit by a single gaussian office, indicating that the events arose from a common underlying process.
- Third, these events could only be recorded in the vicinity of the synaptic junction.
- 4th, they were blocked by curare.
- Fifth, they were enhanced past neostigmine.
Based on these considerations, Katz called these events miniature endplate potentials or MEPPs. They appeared very similar to endplate potentials, but they were only virtually 0.5 mV in aamplitude compared to the fifty mV amplitude of the normal EPP. Katz suggested that MEPPs were due to the spontaneous and random release of ACh. This idea intuitively makes practiced sense. If there is an abundance of ACh in the presynaptic concluding, perhaps some will leak out and diffuse beyond the cleft, demark to ACh receptors, and produce a small potential alter. ACh is likely to exist spontaneously released occasionally because there is a basal level of calcium in the presynaptic terminal. Each vesicle actually contains enough transmitter to open up nearly one,000 individual ACh-sensitive channels. Therefore, because the MEPP is about 0.v mV in amplitude, the opening of a single channel produces a potential of well-nigh 0.5 μV.
(The designation MEPP has a very specific significant. It refers to those small endplate potentials that occur randomly in the absence of whatsoever stimulation. For example, small endplate potentials (EPPs) can be recorded in the presence of curare or low levels of extracellular Caii+ , but they are not MEPPs.)
Katz suggested, as a issue of the experiment illustrated in Figure five.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 nearly 0.5 mV. The release of 100 of those vesicles at the same time could produce a potential which is 100 times as great (fifty mV).
The analogy beneath (Figure five.iv) shows one of these vesicles in the procedure 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 most x,000 molecules of transmitter. Vesicles ready to exist released are establish in a region near the presynaptic concluding membrane called the readily releasable pool. Newly synthesized vesicles are institute in the storage or reserve pool. The process by which a vesicle migrates from the reserve pool to the readily releasable pool is called mobilization. After fusing with the membrane and releasing its contents, the membrane is recycled to form new synaptic vesicles. This procedure is called recycling. Additional details of this process are found in Chapter x.
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. Considering less Ca2+ is in the extracellular medium, less Ca2+ will be bachelor to enter through the voltage-dependent Ca2+ channels. At the pointer, the electric shock was delivered to the motor axon. Eight successive stimuli were delivered to the presynaptic concluding. 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 i.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 i.half dozen mV. Figure 5.5 is a plot of the number of times an EPP of diverse amplitudes was observed. Katz noticed that the amplitude of the smallest EPP that could be evoked was the same amplitude (0.5 mV) equally the amplitude of the MEPP.
Based on these results Katz proposed the quantal hypothesis for chemical synaptic manual. An action potential in the presynaptic cell produces an influx of Ca2+which promotes the exocytosis of synaptic vesicles from the presynaptic terminal. At that place is a statistical variability in the amount of vesicles that can exist released. When the extracellular calcium concentration is low, sometimes at that place is not enough calcium to release any vesicles. At other times, there is enough calcium to crusade the release of one vesicle and other times 2 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 mode. With normal levels of calcium, there is sufficient influx of Ca2+to release most 100 vesicles, which produce an endplate potential (EPP) of about l mV.
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| Figure 5.six |
Test Your Knowledge
- Question ane
- A
- B
- C
- D
- Due east
In a normal, salubrious individual the number of ACh-sensitive channels in a skeletal muscle cell opened equally a result of a single activeness potential in a motor axon would be approximately.
A. one
B. 100
C. 10,000
D. 100,000
E. 10,000,000
In a normal, good for you individual the number of ACh-sensitive channels in a skeletal muscle cell opened every bit a result of a unmarried activeness potential in a motor axon would be approximately.
A. ane This answer is Wrong.
B. 100
C. 10,000
D. 100,000
Eastward. 10,000,000
In a normal, healthy private the number of ACh-sensitive channels in a skeletal muscle cell opened equally a result of a unmarried action potential in a motor axon would be approximately.
A. 1
B. 100 This answer is Incorrect.
C. 10,000
D. 100,000
E. 10,000,000
In a normal, good for you individual the number of ACh-sensitive channels in a skeletal muscle cell opened as a result of a single activity potential in a motor axon would be approximately.
A. 1
B. 100
C. 10,000 This answer is Incorrect.
D. 100,000
E. 10,000,000
In a normal, healthy individual the number of ACh-sensitive channels in a skeletal musculus cell opened as a upshot of a single action potential in a motor axon would exist approximately.
A. 1
B. 100
C. 10,000
D. 100,000 This answer is Correct! The opening of a single ACh-sensitive channel produces a potential change of most 0.5 microvolts. Therefore, it takes almost 1,000 ACh-sensitive channels to produce a potential modify equal to the size of a miniature end-plate potential (MEPP), which has a value of about 0.5 mV. A normal end-plate potential is about 50 mV. Therefore, one needs 100 times the number of channels (i,000) that are needed to produce a MEPP to produce a normal stop-plate potential.
Eastward. x,000,000
In a normal, healthy individual the number of ACh-sensitive channels in a skeletal musculus cell opened as a result of a single activity potential in a motor axon would be approximately.
A. i
B. 100
C. ten,000
D. 100,000
E. 10,000,000 This answer is INCORRECT.
- Question 2
- A
- B
- C
- D
An isolated nerve muscle preparation treated with a moderate dose of curare would be associated with a subtract in the (NOTE: there is more than one correct answer.)
A. Frequency of MEPPs
B. Amplitude of MEPPs
C. Release of transmitter from the terminal of the motor axon triggered by a presynaptic action potential
D. Aamplitude of the EPP
An isolated nerve muscle grooming treated with a moderate dose of curare would be associated with a decrease in the (Notation: in that location is more than one correct answer.)
A. Frequency of MEPPs This answer is INCORRECT. The frequency of MEPPs would not be affected. The frequency of MEPPs is determined strictly by the levels of basal calcium in the presynaptic terminal. Curare is a competitive antagonist of ACh, hence it would bear on the amplitude of the miniature end-plate potential, but non the frequency.
B. Amplitude of MEPPs
C. Release of transmitter from the terminal of the motor axon triggered past a presynaptic action potential
D. Amplitude of the EPP
An isolated nerve muscle grooming treated with a moderate dose of curare would exist associated with a decrease in the (NOTE: there is more than one correct respond.)
A. Frequency of MEPPs
B. Amplitude of MEPPs This answer is Right! Curare is a competitive inhibitor of ACh, hence it volition inhibit or reduce the amplitude of the miniature end-plate potential.
C. Release of transmitter from the final of the motor axon triggered by a presynaptic action potential
D. Aamplitude of the EPP
An isolated nerve musculus preparation treated with a moderate dose of curare would be associated with a decrease in the (NOTE: there is more than one correct reply.)
A. Frequency of MEPPs
B. Amplitude of MEPPs
C. Release of transmitter from the concluding of the motor axon triggered past a presynaptic activity potential This reply is INCORRECT. Curare effects the ACh receptors on the postsynaptic side of the synapse. Hence, information technology will take no effect on the release of transmitter from the presynaptic terminal.
D. Aamplitude of the EPP
An isolated nerve musculus preparation treated with a moderate dose of curare would be associated with a decrease in the (NOTE: at that place is more than 1 correct answer.)
A. Frequency of MEPPs
B. Amplitude of MEPPs
C. Release of transmitter from the concluding of the motor axon triggered past a presynaptic action potential
D. Amplitude of the EPP This answer is CORRECT! Since curare affects the aamplitude of the miniature end-plate potential, it would also bear on the aamplitude of the finish-plate potential through the same mechanisms, competitive inhibition of ACh for its receptor.
- Question 3
- A
- B
- C
- D
An isolated nerve muscle preparation exposed to a depression concentration of extracellular Caii+ would be associated with a decrease in the (NOTE: at that place is more than than one correct answer.)
A. Amplitude of the EPP
B. Release of transmitter from the terminal of the motor axon triggered past a presynaptic action potential
C. Influx of Catwo+ into the presynaptic final
D. Amplitude of MEPPs
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.)
A. Amplitude of the EPP This answer is Correct! The decreased extracellular concentration of calcium results in less calcium entering the presynaptic concluding during an activeness potential. Less transmitter would be released, and there would be a smaller end-plate potential.
B. Release of transmitter from the concluding of the motor axon triggered by a presynaptic action potential
C. Influx of Ca2+ into the presynaptic concluding
D. Amplitude of MEPPs
An isolated nervus muscle preparation exposed to a low concentration of extracellular Ca2+ would be associated with a decrease in the (NOTE: there is more than one right answer.)
A. Aamplitude of the EPP
B. Release of transmitter from the terminal of the motor axon triggered past a presynaptic action potential This answer is Right! The reduced concentration of extracellular calcium would result in decreased influx of calcium into the presynaptic final with an activity potential in the presynaptic concluding. The reduced level of intracellular Ca2+ would pb to decreased release of transmitter.
C. Influx of Ca2+ into the presynaptic terminal
D. Amplitude of MEPPs
An isolated nervus muscle preparation exposed to a low concentration of extracellular Ca2+ would be associated with a subtract in the (Notation: there is more than i correct reply.)
A. Aamplitude of the EPP
B. Release of transmitter from the terminal of the motor axon triggered past a presynaptic activity potential
C. Influx of Caii+ into the presynaptic terminal This answer is Right! Decreased extracellular calcium would lead to decreased influx of calcium through voltage-dependent calcium channels that are opened as a result of a presynaptic action potential.
D. Amplitude of MEPPs
An isolated nerve muscle preparation exposed to a low concentration of extracellular Ca2+ would be associated with a decrease in the (Note: at that place is more than 1 correct answer.)
A. Amplitude of the EPP
B. Release of transmitter from the final of the motor axon triggered by a presynaptic activeness potential
C. Influx of Ca2+ into the presynaptic last
D. Amplitude of MEPPs This answer is INCORRECT.
There would be no change in the amplitude of the miniature end-plate potential. The amplitude of the miniature end-plate potential is dependent upon the amount of transmitter independent in an private vesicle. This would be independent of the Ca influx that occurred during an action potential and contained of the concentration of extracellular calcium.
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