Dexmedetomidine Reduces Presynaptic γ-Aminobutyric Acid Release and Prolongs Postsynaptic Responses in Layer 5 Pyramidal Neurons in the Primary Somatosensory Cortex of Mice.

Dexmedetomidine (DEX) exhibits notable sedative, analgesic, and anesthetic-sparing properties. While growing evidence suggests these effects are linked to the modulation of γ-aminobutyric acid (GABA) system, the precise pre- and postsynaptic mechanisms of DEX action on cortical GABAergic signaling remain unclear. In this study, we applied whole-cell patch-clamp recording to investigate the impact of DEX on GABAergic transmission in layer 5 pyramidal neurons of the mouse primary somatosensory cortex. We recorded spontaneous inhibitory postsynaptic currents (sIPSCs), miniature IPSCs (mIPSCs), and evoked inhibitory postsynaptic potentials (eIPSPs) before and during DEX application. Our findings demonstrated that DEX reduced activity-dependent spontaneous GABAergic transmission, as evidenced by a decrease in sIPSC frequency, while mIPSC frequency was unaffected. eIPSPs were not significantly influenced by DEX either. Additionally, DEX prolonged the kinetics of both sIPSCs and mIPSCs, increasing the rise and decay times of sIPSCs and the decay time of mIPSCs. We proposed that DEX modulated cortical neuronal activity by limiting GABA release and altering GABAA receptor kinetics. Collectively, these results indicated that DEX modulated cortical GABAergic signaling at both presynaptic and postsynaptic sites, which likely underlined its sedative, analgesic, and anesthetic-sparing effects.