Regulation of GABA(A) Receptors Induced by the Activation of L-Type Voltage-Gated Calcium Channels

GABA(A) receptors are pentameric ion channels that mediate most synaptic and tonic extrasynaptic inhibitory transmissions in the central nervous system. There are multiple GABA(A) receptor subtypes constructed from 19 different subunits in mammals that exhibit different regional and subcellular distributions and distinct pharmacological properties. Dysfunctional alterations of GABA(A) receptors are associated with various neuropsychiatric disorders. Short- and long-term plastic changes in GABA(A) receptors can be induced by the activation of different intracellular signaling pathways that are triggered, under physiological and pathological conditions, by calcium entering through voltage-gated calcium channels. This review discusses several mechanisms of regulation of GABA(A) receptor function that result from the activation of L-type voltage gated calcium channels. Calcium influx via these channels activates different signaling cascades that lead to changes in GABA(A) receptor transcription, phosphorylation, trafficking, and synaptic clustering, thus regulating the inhibitory synaptic strength. These plastic mechanisms regulate the interplay of synaptic excitation and inhibition that is crucial for the normal function of neuronal circuits.