Biological Membranes - A. N. Ogurtsov 2012

Electrogenesis of Biomembranes
Mechanisms of Intercellular Signaling
Neuronal Synapses

Synapses between motor Neurons and Skeletal Muscle Cells (neuromuscular junctions) (Figure 154) function as triggers (each Action Potential in the presynaptic neuron triggers the contraction of a muscle Cell) because the action potential in the presynaptic cell stimulates the secretion of sufficient acetylcholine to depolarize the postsynaptic cell membrane.

Synapses between neurons operate differently. Let us examine the synapse between a sensory pain neuron and an association (Relay) neuron (Figure 159).

At this synapse, a single action potential impulse in the presynaptic axon terminal of the sensory neuron stimulates the neurosecretion of a small quantity of glutamic acid neurotransmitter molecules into the synaptic cleft. Although their binding to glutamate receptors on the postsynaptic membrane of the association neuron depolarizes this membrane, its amplitude remains below the threshold required to generate an action potential.

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Figure 159 - A single impulse in a sensory neuron is unable to stimulate an action potential in an association neuron

Consequently, once glutamic acid is cleared from the synaptic cleft, the Membrane Potential of the postsynaptic membrane returns to its resting value.

Conversely, if impulses arrive at the dendrites of the association neuron simultaneously from several sensory neurons (Figure 160), this spatial summation combines the "doses" of glutamic acid. Membrane depolarization exceeds the threshold, an action potential is triggered in the postsynaptic association neuron, and the Organism perceives pain.

Figure 160 - Spatial summation at the synapse

An action potential can also be generated in the postsynaptic association neuron As a result of initiation by a single presynaptic neuron. This occurs when a sensory receptor is intensely excited, producing a high-frequency train of impulses with a short inter-pulse interval (Figure 161).

For example, in the case of a pain receptor (Figure 137), pricking a finger with a needle stimulates only a single receptor in the finger, but the excitation intensity is so high that a continuous sequence of action potential impulses is triggered in the receptor.

Each of these impulses stimulates the release of sodium glutamate into the synapse. If the intervals between successive impulses in this train are sufficiently short, temporal summation of depolarizations occurs, the membrane potential reaches the threshold value, and an action potential is triggered. This potential propagates along the axon of the association neuron, transmitting information about the event to the Brain (Figure 161).

Figure 161 - Temporal summation at the synapse

When summing excitation impulses from multiple presynaptic neurons onto a postsynaptic neuron—particularly within the brain—more complex scenarios can arise, as neurons respond differently to various types of Neurotransmitters originating from different neurons.

Consider, for instance, a situation where an association neuron forms six synapses with presynaptic neurons that secrete sodium glutamate into the synaptic clefts, and one synapse with the axon of a neuron that uses γ-aminobutyric acid (GABA, Figure 152) as a neurotransmitter (Figure 162).

Figure 162 - Inhibition by a GABA synapse

The γ-aminobutyric acid receptor is a Ligand-gated protein channel for Cl^- ions. In our example, the postsynaptic neuron possesses receptors for both glutamate and GABA.

Let us examine how the postsynaptic neuron will respond to various combinations of signals arriving from the presynaptic neurons.

In scenario (A) in Figure 162, an action potential (2) in the GABA-secreting axon releases GABA, which opens the GABA receptors on the postsynaptic membrane. Although chloride anions can now cross the membrane, the electrochemical potentials of Cl^- ions are equal on both sides of the membrane, and the concentration gradient is balanced by the electrical gradient. Consequently, the opening of GABA channels does not alter the membrane potential.

In scenario (B), action potential impulses (1) arrive simultaneously at the synapses of six glutamate-secreting axons. In this case, sufficient neurotransmitter molecules are released into the synaptic clefts to depolarize the postsynaptic neuron membrane and generate an action potential within it.

Receptors whose binding to neurotransmitters leads to the generation of an action potential are called excitatory receptors. Neuronal excitatory receptors function as channels for Na⁺ ions. In our example, the glutamate-gated receptors serve this excitatory role.

In scenario (C), excitatory impulses arrive simultaneously from both the six glutamate-secreting axons (1) and the GABA-secreting axon (2). As in scenario (B), the same amount of sodium glutamate is secreted into the synaptic clefts, and the same number of sodium ions pass through the glutamate-gated receptors, tending to depolarize the postsynaptic membrane.

However, because the postsynaptic membrane potential is no longer at its resting level, the equilibrium condition for chloride ions is disrupted, and Cl^- ions flow inward across the membrane into the postsynaptic neuron via the GABA receptor channels.

The influx of chloride anions partially neutralizes the excessive positive potential generated by the inward flow of sodium cations into the postsynaptic neuron through glutamate receptor channels. Consequently, postsynaptic depolarization fails to reach the critical threshold, and an action potential is not triggered.

In our example, the activation of GABA receptors leads to the inhibition of Nerve Impulse generation.

Receptors whose neurotransmitter binding results in the inhibition of an action potential are called inhibitory receptors. Neuronal inhibitory receptors function as channels for Cl^- ions entering The Cell or K⁺ ions exiting the cell. In our example, the GABA receptors act as inhibitory receptors.

Sedative medications, such as Valium, act on GABA receptors by facilitating channel opening. Neurons affected by Valium undergo depolarization less frequently; consequently, Valium dampens brain neuron activity, thereby calming the patient.

METABOLISM/35.html">Selection/41.html">Review Questions and Exercises

1. What are Gap Junctions?

2. What is The Structure of gap junctions?

3. Under what circumstances must Intercellular junctions be gap junctions?

4. What are Transmitters?

5. How do transmitters differ in their lifetime? Give Examples.

6. What are paracrine transmitters?

7. What Three types of receptors for transmitters are distinguished?

8. Which transmitter binds to the membrane a-adrenergic receptor?

9. Which transmitter binds to the membrane ß-adrenergic receptor?

10. What intracellular transmitter receptors do you know?

11. What neurotransmitters do you know?

12. What are the two differences between neurosecretion and other secretory mechanisms?

13. How does the recycling of acetylcholine from the synaptic cleft back into the presynaptic axon differ from the recycling of other neurotransmitters?

14. What Two Types of synaptic vesicles are distinguished in axon terminals?

15. Which intercellular junction is called a Neuromuscular Junction?

16. Which four types of Ion Channels and in what sequence mediate Muscle contraction?

17. What subunits make up the nicotinic Acetylcholine Receptor?

18. What subunit Conformations ensure the functioning of the nicotinic acetylcholine receptor?

19. Which neurotransmitter is secreted by vasoconstrictor nerves?

20. Which neurotransmitter is secreted by vasodilator nerves?

21. Which enzyme is most frequently utilized by cAMP for metabolic action in signaling pathways?

22. Which enzyme is most frequently utilized by cGMP for metabolic action in signaling pathways?

23. Why is nitric oxide considered a paracrine transmitter?

24. What are the three main isoforms of nitric oxide synthase (NOS)?

25. What is the functional difference between neuromuscular junctions (synapses between motor neurons and skeletal muscle cells) and synapses between two neurons?

26. How does spatial summation of nerve impulses occur at a neuronal synapse?

27. How does temporal summation of nerve impulses occur at a neuronal synapse?

28. Which receptors are classified as excitatory?

29. Which receptors are classified as inhibitory?

30. What are the Similarities and differences between the processes occurring at excitatory versus inhibitory receptor synapses with a neuron?