INFLAMMATORY MEDIATOR-INDUCED MODULATION OF GABA(A) CURRENTS IN HUMAN SENSORY NEURONS

摘要

The purpose of the present study was to characterize the properties of A-type GABA receptor (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 mu M), and persistent currents were activated by the d-subunit-preferring agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (THIP). The GABA current equilibrium potential was similar to 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. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.