Question

Suppose you are provided with an isolated nerve-muscle preparation in order to study synaptic transmission. In one of your experiments, you give this preparation a drug that blocks voltageregulated \(\mathrm{Ca}^{+}\)channels; in another, you give tetanus toxin to the preparation. How will synaptic transmission be affected in each experiment?

Short answer

In the first experiment, blocking voltage-regulated Ca^2+ channels disrupts synaptic transmission by preventing the influx of Ca^2+ ions, which impairs the release of neurotransmitters and the communication between nerve and muscle cells. In the second experiment, tetanus toxin impairs the release of inhibitory neurotransmitters, resulting in a loss of inhibitory control and increased excitatory activity, ultimately leading to excessive muscle contraction and spastic paralysis.

Step-by-step solution

In a normal synaptic transmission, an action potential arrives at the presynaptic terminal, causing the voltage-regulated Ca^2+ channels to open. The influx of Ca^2+ ions triggers the release of neurotransmitters from synaptic vesicles into the synaptic cleft. The neurotransmitters then bind to receptors on the postsynaptic membrane, leading to the generation of a postsynaptic potential. The role of Ca^2+ ions in this process is crucial for the release of neurotransmitters. #Step 2: Explain the effect of blocking voltage-regulated Ca^2+ channels#

In the first experiment, the drug blocks voltage-regulated Ca^2+ channels in the presynaptic terminal. As a result, when an action potential arrives at the terminal, these channels remain closed, and Ca^2+ ions do not enter the terminal. This means that neurotransmitter release is impaired or blocked altogether. Consequently, synaptic transmission is disrupted or stopped, ultimately affecting the ability of the nerve impulse to be transmitted to the muscle cell. #Step 3: Understand the effect of tetanus toxin on synaptic transmission#

Tetanus toxin is a neurotoxin produced by the bacterium Clostridium tetani, which specifically targets inhibitory interneurons in the central nervous system. The toxin cleaves proteins involved in the release of inhibitory neurotransmitters, such as GABA and glycine. As a result, the inhibitory synapses become less effective or nonfunctional. #Step 4: Explain the effect of tetanus toxin on the nerve-muscle preparation#

In the second experiment, tetanus toxin is applied to the nerve-muscle preparation. Since inhibitory neurotransmitter release is affected, the overall inhibition in the synaptic transmission is reduced or lost. This leads to increased excitation of the postsynaptic cells, ultimately causing excessive muscle contraction and spastic paralysis. Therefore, synaptic transmission in this preparation will be affected by a loss of inhibitory control and an increase in excitatory activity.

Key concepts

Voltage-Regulated Ca2+ Channels

Voltage-regulated Ca\(^{2+}\) channels play a pivotal role in the process of synaptic transmission. These channels reside in the membrane of the presynaptic neuron, and their primary function is to regulate the influx of calcium ions. When an action potential travels down the neuron and reaches the presynaptic terminal, it causes these channels to open. This opening allows Ca\(^{2+}\) ions to enter the neuron from the extracellular space.
The entry of calcium ions into the neuron is a critical trigger for the release of neurotransmitters from synaptic vesicles. The Ca\(^{2+}\) ions facilitate this release by prompting synaptic vesicles to fuse with the presynaptic membrane. These vesicles then expel neurotransmitters into the synaptic cleft, where they can bind to receptors on the postsynaptic neuron. This binding is what ultimately leads to the generation of a postsynaptic potential. Without the influx of Ca\(^{2+}\), neurotransmitter release would not occur, halting synaptic transmission.
In experiments where voltage-regulated Ca\(^{2+}\) channels are blocked by drugs, the following typically occurs:

• The action potential reaches the presynaptic terminal, but the channels remain closed.
• Without Ca\(^{2+}\) entry, neurotransmitter release is impaired.
• Synaptic transmission is disrupted, hindering nerve impulse propagation to the muscle cell.

Thus, these channels are essential for effective communication between neurons.

Neurotransmitter Release

Neurotransmitter release is central to how neurons communicate with each other. After calcium ions enter the presynaptic terminal via voltage-regulated Ca\(^{2+}\) channels, they trigger the release of neurotransmitters stored in synaptic vesicles. This process occurs through a mechanism known as exocytosis.
In exocytosis, the synaptic vesicles containing neurotransmitters migrate toward the presynaptic membrane. The vesicles fuse with the membrane, leading to the release of neurotransmitters into the synaptic cleft. Once released, these chemical messengers diffuse across the cleft and bind to receptors on the postsynaptic neuron. This binding can either excite or inhibit the postsynaptic neuron, depending on the nature of the neurotransmitters and receptors involved.
Key steps in neurotransmitter release include:

• Action potential arrival and opening of Ca\(^{2+}\) channels.
• Influx of Ca\(^{2+}\) and fusion of vesicles with the presynaptic membrane.
• Release of neurotransmitters into the synaptic cleft.
• Binding and activation of postsynaptic receptors to generate a response.

Therefore, the process of neurotransmitter release is indispensable for synaptic transmission, affecting everything from muscle movement to mood regulation.

Tetanus Toxin Effects

Tetanus toxin is a potent neurotoxin produced by the bacterium Clostridium tetani. It specifically disrupts synaptic transmission by targeting inhibitory neurons in the central nervous system. The toxin interferes with the release of inhibitory neurotransmitters like GABA (gamma-aminobutyric acid) and glycine. It does this by cleaving proteins involved in neurotransmitter release.
In a nerve-muscle preparation, the presence of tetanus toxin leads to a significant reduction in inhibitory control. As these inhibitory synapses become nonfunctional, fewer inhibitory signals are sent to the postsynaptic neurons. This reduction in inhibition leads to unopposed excitation, causing muscle cells to contract excessively. The end result is spastic paralysis, characterized by continuous muscle contraction.
Effects of tetanus toxin include:

• Blocking of inhibitory neurotransmitter release in the central nervous system.
• Reduction or loss of synaptic inhibition.
• Increased excitation and excessive muscle contraction due to inadequate inhibition.

Understanding the effects of tetanus toxin highlights the delicate balance of excitatory and inhibitory signals necessary for normal muscular and neuronal function.