Abstract

GABAA receptors (GABAA_AA) are ligand-gated chloride channels mediating fast and slow inhibitory signaling in the nervous system. δ-Subunit-containing receptors exhibit high GABA affinity, extrasynaptic localization and marked sensitivity to endogenous neurosteroids, generating tonic inhibitory currents that regulate baseline excitability in the CNS. Emerging evidence indicates that these receptors are also expressed in peripheral tissues, including the skin, retina, olfactory epithelium, gastrointestinal tract, kidney, immune cells and reproductive organs. They are notably absent in the heart, highlighting a selective role in sensory modulation. We hypothesize that δ-subunit-containing GABAA_AA receptors mediate local and systemic sensory inhibition through tonic, extrasynaptic signaling and neurosteroiddependent modulation. This network stabilizes neuronal and sensory activity, prevents hyperexcitability and may coordinate body-wide sensory responsiveness. Dysregulation of this system could contribute to disorders such as chronic pain, inflammatory skin disease, olfactory dysfunction and neuropsychiatric conditions.

Keywords:δ-subunit GABAA receptors; Tonic inhibition; Extrasynaptic signaling; Neurosteroids; Peripheral sensory modulation; CNS regulation; Sensory hyperexcitability