Inflammatory mediator-induced modulation of GABA _A currents in human sensory neurons

Abstract

The purpose of the present study was to characterize the properties of GABA _A receptor currents in human sensory neurons. Neurons were obtained from adult organ donors. GABA _A currents were recorded in isolated neurons. Both large inactivating low affinity currents and smaller persistent high affinity currents were present in all of the 129 neurons studied from 15 donors. The kinetics of human GABA _A currents were slower than those in rat sensory neurons. GABA currents were completely blocked by bicuculline (10 µM), and persistent currents were activated by the δ-subunit preferring agonist, THIP. The GABA current equilibrium potential was ~20 mV more hyperpolarized than in rat neurons. Both low and high affinity currents were increased by inflammatory mediators but via different second messenger pathways. These results highlight potentially important species differences in the properties of ion channels present in their native environment and suggest the use of human sensory neurons may be a valuable tool to test compounds prior to use in humans.