How do GABA and glycine function as inhibitory neurotransmitters?

Sourav PanSeptember 23, 2024

Answered

GABA (gamma-aminobutyric acid) and glycine are two key inhibitory neurotransmitters in the central nervous system (CNS) that play crucial roles in regulating neuronal excitability and maintaining the balance between excitation and inhibition. Here’s how they function:

1. Mechanism of Action:

• GABA:
  • GABA primarily acts through two types of receptors: GABAA​ and GABAB​.
    • GABAA​ Receptors: These are ionotropic receptors that, when activated by GABA, open chloride (Cl⁻) channels. The influx of Cl⁻ ions into the neuron leads to hyperpolarization of the postsynaptic membrane, making it less likely to fire an action potential. This rapid inhibitory effect is crucial for fast synaptic transmission.
    • GABAB​ Receptors: These are metabotropic receptors that activate G-proteins, leading to the opening of potassium (K⁺) channels and the closing of calcium (Ca²⁺) channels. This results in a slower, longer-lasting inhibitory effect by hyperpolarizing the neuron and reducing neurotransmitter release from presynaptic terminals.
• Glycine:
  • Glycine primarily acts through glycine receptors, which are also ionotropic and function similarly to GABAA​ receptors. When glycine binds to its receptor, it opens Cl⁻ channels, allowing Cl⁻ ions to flow into the neuron, leading to hyperpolarization and inhibition of action potential generation. Glycine is particularly important in the spinal cord and brainstem, where it helps regulate motor control and sensory processing.

2. Role in Inhibition:

• Both GABA and glycine serve to inhibit neuronal activity, which is essential for:
  • Preventing Overactivity: By inhibiting excitatory signals, GABA and glycine help prevent excessive neuronal firing, which can lead to conditions such as seizures or anxiety disorders.
  • Modulating Synaptic Integration: Inhibitory inputs from GABA and glycine can shape the overall response of a neuron to excitatory inputs, allowing for more precise control of neuronal output. For example, inhibitory synapses are often located near the axon hillock, where they can effectively influence whether the neuron will fire an action potential in response to excitatory inputs.

3. Clinical Relevance:

• Dysregulation of GABA and glycine signaling is associated with various neurological and psychiatric disorders. For instance:
  • GABA: Reduced GABAergic activity is linked to anxiety, depression, and epilepsy. Many anxiolytic drugs (e.g., benzodiazepines) enhance GABA activity to promote inhibition and reduce anxiety.
  • Glycine: Abnormal glycine signaling can contribute to conditions such as hyperekplexia (startle disease) and certain types of spasticity.