Mechanisms of sleep induction by GABA(A) receptor agonists.

TL;DRAbstract

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. GABA(A) receptors are pentameric complexes that function as ligand-gated chloride ion channels. Two types of inhibitory neurotransmission are mediated via GABA(A) receptors. Phasic inhibition results from the activation of receptors at the synapse by intermittent release of high concentrations of GABA from presynaptic terminals. Tonic inhibition, in contrast, is mediated by the continuous activation of receptors located outside the synaptic cleft by low concentrations of ambient GABA. These "extrasynaptic" receptors have a higher affinity for GABA and slower rates of desensitization and deactivation than do the classical "synaptic" receptors. A variety of subunit families make up GABA(A) receptors; a total of 19 distinct subunits have been cloned. This diversity in subunit composition results in substantial anatomical, functional, and pharmacologic heterogeneity. Receptors c

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