Answer
Gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the central nervous system. When GABA is released at an inhibitory synapse and binds to its receptors on the postsynaptic neuron, it typically leads to the inhibition of the postsynaptic neuron's activity. Here's how GABA inhibits a postsynaptic neuron:
1. **Release of GABA:** GABA is synthesized and stored in vesicles within the presynaptic terminal of an inhibitory neuron. When an action potential arrives at the presynaptic terminal, voltage-gated calcium channels open, allowing calcium ions (Ca2+) to enter.
2. **Exocytosis of GABA:** The influx of calcium ions triggers the fusion of GABA-containing vesicles with the presynaptic membrane. This release of GABA molecules into the synaptic cleft is a calcium-dependent process.
3. **Binding to GABA Receptors:** GABA diffuses across the synaptic cleft and binds to specific GABA receptors located on the postsynaptic membrane. The two main types of GABA receptors are GABA-A receptors and GABA-B receptors.
- **GABA-A Receptors:** These are ligand-gated ion channels that, when activated by GABA binding, allow the flow of chloride ions (Cl-) into the postsynaptic neuron. GABA-A receptors are typically found at synapses between neurons.
- **GABA-B Receptors:** These are G-protein-coupled receptors. When GABA binds to GABA-B receptors, it activates intracellular signaling pathways through G-proteins, which can lead to various inhibitory effects, such as the opening of potassium channels or the inhibition of calcium channels. GABA-B receptors are often found at both neuronal synapses and on other cell types, including glial cells.
4. **Chloride Ion Influx:** In the case of GABA-A receptors, GABA binding causes the chloride ion channels to open. Chloride ions flow into the postsynaptic neuron, leading to membrane hyperpolarization, where the inside of the neuron becomes more negative compared to its resting state.
5. **Hyperpolarization and Inhibition:** The hyperpolarization of the postsynaptic membrane makes it less likely for the neuron to reach its threshold potential required for generating an action potential. In other words, GABA-induced hyperpolarization inhibits the neuron by making it more resistant to excitation. This is known as an inhibitory postsynaptic potential (IPSP).
6. **Summation of Signals:** In a neuron, both excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) are integrated. If the net effect of IPSPs outweighs that of EPSPs, the neuron is less likely to fire an action potential.
Overall, GABA's inhibitory actions are critical for maintaining the balance of excitation and inhibition in the nervous system, allowing for precise control of neuronal activity and preventing excessive or uncontrolled firing of neurons. GABAergic inhibition is essential for functions such as controlling anxiety, reducing seizure activity, and regulating the overall excitability of neural circuits.
Work Step by Step
Gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the central nervous system. When GABA is released at an inhibitory synapse and binds to its receptors on the postsynaptic neuron, it typically leads to the inhibition of the postsynaptic neuron's activity. Here's how GABA inhibits a postsynaptic neuron:
1. **Release of GABA:** GABA is synthesized and stored in vesicles within the presynaptic terminal of an inhibitory neuron. When an action potential arrives at the presynaptic terminal, voltage-gated calcium channels open, allowing calcium ions (Ca2+) to enter.
2. **Exocytosis of GABA:** The influx of calcium ions triggers the fusion of GABA-containing vesicles with the presynaptic membrane. This release of GABA molecules into the synaptic cleft is a calcium-dependent process.
3. **Binding to GABA Receptors:** GABA diffuses across the synaptic cleft and binds to specific GABA receptors located on the postsynaptic membrane. The two main types of GABA receptors are GABA-A receptors and GABA-B receptors.
- **GABA-A Receptors:** These are ligand-gated ion channels that, when activated by GABA binding, allow the flow of chloride ions (Cl-) into the postsynaptic neuron. GABA-A receptors are typically found at synapses between neurons.
- **GABA-B Receptors:** These are G-protein-coupled receptors. When GABA binds to GABA-B receptors, it activates intracellular signaling pathways through G-proteins, which can lead to various inhibitory effects, such as the opening of potassium channels or the inhibition of calcium channels. GABA-B receptors are often found at both neuronal synapses and on other cell types, including glial cells.
4. **Chloride Ion Influx:** In the case of GABA-A receptors, GABA binding causes the chloride ion channels to open. Chloride ions flow into the postsynaptic neuron, leading to membrane hyperpolarization, where the inside of the neuron becomes more negative compared to its resting state.
5. **Hyperpolarization and Inhibition:** The hyperpolarization of the postsynaptic membrane makes it less likely for the neuron to reach its threshold potential required for generating an action potential. In other words, GABA-induced hyperpolarization inhibits the neuron by making it more resistant to excitation. This is known as an inhibitory postsynaptic potential (IPSP).
6. **Summation of Signals:** In a neuron, both excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) are integrated. If the net effect of IPSPs outweighs that of EPSPs, the neuron is less likely to fire an action potential.
Overall, GABA's inhibitory actions are critical for maintaining the balance of excitation and inhibition in the nervous system, allowing for precise control of neuronal activity and preventing excessive or uncontrolled firing of neurons. GABAergic inhibition is essential for functions such as controlling anxiety, reducing seizure activity, and regulating the overall excitability of neural circuits.
