glycinergiske

Glycinergic, or glycinergic signaling, refers to neurons and synapses in which glycine is the primary inhibitory neurotransmitter of the central nervous system. In glycinergic synapses, glycine is released from presynaptic terminals and binds to postsynaptic glycine receptors, opening chloride channels and producing hyperpolarization that reduces neuronal excitability.

The main receptor mediating glycinergic inhibition is the glycine receptor (GlyR), a pentameric ligand-gated chloride channel. In humans, GlyR subunits are encoded by GLRA1–GLRA4 and GLRB. Receptors typically contain combinations of α subunits (α1–α4) with a β subunit, and they are concentrated at motor and sensory pathways, especially in the spinal cord and brainstem, with significant roles in reflexes and motor coordination. The β subunit helps anchor GlyRs at synapses through interaction with the scaffolding protein gephyrin.

Glycinergic transmission relies on the recycling of glycine by transporter proteins. GlyT2 (neuronal) is primarily responsible for reuptake into presynaptic terminals, supporting rapid synaptic transmission, while GlyT1 (glial) modulates glycine levels in the extracellular space, including at non-glycinergic synapses and NMDA receptors.

Clinical significance includes hyperekplexia (startle disease), caused by mutations in GLRA1 or GLRB, and sometimes SLC6A5 (GlyT2). Symptoms include an excessive startle response and muscle rigidity; treatment may involve benzodiazepines such as clonazepam. Strychnine, a famous glycine receptor antagonist, produces severe convulsions by blocking inhibitory glycinergic signaling.

Glycinergic mechanisms also intersect with excitatory signaling, as glycine can act as a co-agonist at NMDA receptors under certain conditions, highlighting the system’s complex role in modulating CNS activity.