The synapse is a specialized structure that allows one neuron to communicate with another neuron or a muscle cell. There are billions of nerve cells in the brain and each nerve cell can make and receive up to 10,000 synaptic connections with other nerve cells. Also, the strength of the synapse is modifiable. Changes in the strength of synapses endow the nervous system with the ability to store information.
Figure 4.1 (see enlarged view) |
Anatomy of the Neuromuscular Junction
The synapse for which most is known is the one formed between a spinal motor neuron and a skeletal muscle cell. Historically, it has been studied extensively because it is relatively easy to analyze. However, the basic properties of synaptic transmission at the skeletal neuromuscular junction are very similar to the process of synaptic transmission in the central nervous system. Consequently, an understanding of this synapse leads to an understanding of the others. Therefore, we will first discuss the process of synaptic transmission at the skeletal neuromuscular junction.
The features of the synaptic junction at the neuromuscular junction are shown in the figure at left. Skeletal muscle fibers are innervated by motor neurons whose cell bodies are located in the ventral horn of the spinal cord. The terminal region of the axon gives rise to very fine processes that run along skeletal muscle cells. Along these processes are specialized structures known as synapses. The particular synapse made between a spinal motor neuron and skeletal muscle cell is called the motor endplate because of its specific structure.
The synapse at the neuromuscular junction has three characteristic features of chemical synapses in the nervous system. First, there is a distinct separation between the presynaptic and the postsynaptic membrane. The space between the two is known as the synaptic cleft. The space tells us there must be some intermediary signaling mechanism between the presynaptic neuron and the postsynaptic neuron in order to have information flow across the synaptic cleft. Second, there is a characteristic high density of small spherical vesicles. These synaptic vesicles contain neurotransmitter substances. Synapses are also associated with a high density of mitochondria. Third, in most cases, there is a characteristic thickening of the postsynaptic membrane, which is due at least in part to the fact that the postsynaptic membrane has a high density of specialized receptors that bind the chemical transmitter substances released from the presynaptic neuron. Additional details on the morphological features of synaptic junctions is provided in Chapter 8, Part 7 and Chapter 10, Part 4.
Physiology of Synaptic Transmission at the Neuromuscular Junction
Figure 4.2 |
The figure at the right illustrates in a very schematic way how it is possible to study the physiology of synaptic transmission at the skeletal neuromuscular junction in great detail. A piece of muscle and its attached nerve are placed in a small experimental chamber filled with an appropriate Ringer solution. The resting potential of the muscle cell is recorded with a microelectrode. Electrodes are also placed on the surface of the nerve axon. Brief electric shocks cause action potentials to be initiated, which propagate to the synaptic terminal.
The figure below illustrates two types of potential changes that were recorded in such an isolated nerve-muscle preparation. The experiment also illustrates the properties of a powerful drug, curare, which has proven to be very useful in studying the process of synaptic transmission at the skeletal neuromuscular junction. Part A illustrates the sequence of potential changes recorded in the muscle cell as a result of stimulating the motor axon. The arrow indicates the point in time when the shock is delivered to the motor axon. Note that there is a quiescent period of time after the shock. The delay is due to the time it takes for the action potential in the motor axon to propagate from its site of initiation. After the delay, there are two types of potentials recorded in the muscle cell. First, there is a relatively slowly changing potential that will be the focus of the following discussion. If that slow initial potential is sufficiently large, as it normally is in skeletal muscle cells, a second potential, an action potential, is elicited in the muscle cell.
Figure 4.3 |
Action potentials in skeletal muscle cells are due to ionic mechanisms similar to those discussed previously. Specifically, there is a voltage-dependent change in Na+ permeability followed by a delayed increase in K+ permeability. (For smooth muscle cells and cardiac muscle cells the ionic mechanisms are different, however.)
The underlying event that triggers the action potential can be revealed by taking advantage of curare, an arrow poison used by some South American Indians. A low dose of curare (Part B) reduces the underlying event, but it is still not sufficiently reduced to fall below threshold. If a somewhat higher dose of curare is delivered (Part C), the slow underlying event becomes subthreshold. The underlying signal is known as the endplate potential (EPP) because it is a potential change recorded at the motor endplate. Generally, it is known as an excitatory postsynaptic potential (EPSP).
Curare blocks the endplate potential because it is a competitive inhibitor of acetylcholine (ACh), the transmitter released at the presynaptic terminal. Curare does not block the voltage-dependent Na+ conductance or the voltage-dependent K+ conductance that underlies the muscle action potential. Curare affects the stimulus (the EPSP) which normally leads to the initiation of the muscle action potential. An animal that is poisoned with curare will asphyxiate because the process of neuromuscular transmission at respiratory muscles is blocked.
Normally, the magnitude of the endplate potential is quite large. Indeed, the amplitude of the endplate potential is about 50 mV, but only about 30 mV is needed to reach threshold. The extra 20 mV is called the safety factor. Therefore, even if the endplate potential were to become somewhat smaller (e.g., 40 mV in amplitude) because of fatigue, the EPP would reach threshold and the one-to-one relationship between an action potential in the motor axon and an action potential in the muscle cell would be preserved.
Figure 4.4 |
Propagation of the EPP
What are the properties of the EPP and how does it compare with the properties of the action potential?
Is the endplate potential due to a voltage-dependent change in Na+ and K+ permeabilities like the action potential?
Is the endplate potential propagated in an all-or-nothing fashion like the action potential?
The figure on the right illustrates an experiment that examines the propagation of the endplate potential. The muscle fiber is impaled repeatedly with electrodes at 1 mm intervals. (Note that the endplate potential is small because this experiment is done in the presence of a low concentration of curare so the endplate potential can be recorded without the complications of triggering an action potential.) The endplate potential is not propagated in an all-or-nothing fashion. It does spread along the muscle, but it does so with decrement. Thus, the spread of the endplate potential from its site of initiation to other sites along the muscle cell occurs passively and with decrement, just as a subthreshold potential change in one portion of the axon spreads along the axon, or just as a change in temperature at one point on a metal rod spreads along the rod.
