Two types of GABAergic miniature inhibitory postsynaptic currents in mouse substantia gelatinosa neurons

The physiological and pharmacological properties of γ-aminobutyric acid (GABA)ergic miniature inhibitory postsynaptic currents (mIPSCs) were investigated in substantia gelatinosa neurons of mouse spinal cord using whole-cell patch clamp recordings. Two cell populations were pharmacologically identified based on the effect of propofol (10 μM) on the mIPSC decay kinetics: those exhibiting propofol-sensitive mIPSCs, with a slow decay kinetic (mIPSCSLOW), and those exhibiting propofol-resistant mIPSCs, with a fast decay kinetic (mIPSCFAST) (decay time constants of 14.2 ± 0.7 and 7.4 ± 0.8 ms, respectively). The frequency and amplitude of both types of mIPSCs were not affected by propofol. Miniature IPSCFAST showed midazolam insensitivity, while midazolam prolonged the decay phase of mIPSCSLOW without modulation of the frequency and amplitude. Exogenous GABA-evoked responses in the neurons with mIPSCSLOW were potentiated by propofol, while those in neurons with mIPSCFAST were unaffected by propofol. Furthermore, non-stationary noise analysis of the two kinetically and pharmacologically distinct mIPSCs revealed different conductance of GABAA receptor channels underlying the synaptic events. Pharmacological responses to propofol and midazolam suggested that mIPSCFAST and mIPSCSLOW in substantia gelatinosa neurons can be mediated by GABAA receptors with different subunit compositions.