TY - JOUR T1 - Synaptic-type α1β2γ2L GABAA Receptors Produce Large Persistent Currents in the Presence of Ambient GABA and Anesthetic Drugs JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.114.096453 SP - mol.114.096453 AU - Ping Li AU - Gustav Akk Y1 - 2015/01/01 UR - http://molpharm.aspetjournals.org/content/early/2015/02/09/mol.114.096453.abstract N2 - Synaptic GABAA receptors respond to synaptically-released GABA and are considered to be unaffected by the low levels of ambient transmitter in the brain. We show that synaptic-type α1β2γ2L GABAA receptors expressed in HEK 293 cells respond with large steady-state currents to combinations of a low concentration (0.5 μM) of GABA and clinically used GABAergic modulators propofol, etomidate, pentobarbital, or the steroid alphaxalone. At a maximally effective concentration of modulator, the current levels at the end of 2 min applications of drug combinations were over 10% of the peak response to 50 μM GABA. In the absence of modulators, 0.5 μM GABA generated a steady-state response of 1% of the peak response to 50 μM GABA. The concentration-response curves for enhancement of steady-state currents by propofol, etomidate, pentobarbital, or alphaxalone were at lower drug concentrations compared to concentration-response relationships for enhancement of peak responses. We propose that modulation of tonically-activated synaptic-type GABAA receptors contributes to the clinical actions of sedative drugs. ER -