TY - JOUR
T1 - Isoflurane slows inactivation kinetics of rat recombinant α1β2γ2L GABAA receptors
T2 - Enhancement of GABAergic transmission despite an open-channel block
AU - Hapfelmeier, Gerhard
AU - Haseneder, Rainer
AU - Eder, Matthias
AU - Adelsberger, Helmuth
AU - Kochs, Eberhard
AU - Rammes, Gerhard
AU - Zieglgänsberger, Walter
PY - 2001/7/13
Y1 - 2001/7/13
N2 - Recombinant α1β2γ2L γ-aminobutyric acid (A) receptor (GABAAR) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10-4 M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABAAR-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.
AB - Recombinant α1β2γ2L γ-aminobutyric acid (A) receptor (GABAAR) channels expressed in human embryonic kidney (HEK293) cells were used for patch-clamp experiments. The currents activated by brief pulses of GABA (10-4 M) applied with a device for fast solution exchange to cells clamped in the whole-cell configuration mimicked GABAAR-mediated inhibitory postsynaptic currents. Isoflurane (ISO) at clinically relevant concentrations (0.6 mM) decreased the amplitude and prolonged the decay of the GABA-evoked response. To further detail the mechanism underlying the prolonged decay time, we made simulations based on these measurements. These simulations suggest that ISO slows the rate of GABA unbinding from the receptor. Under these conditions, ISO increases the GABA-induced charge transfer and, thus, could enhance GABAergic inhibition despite the concomitant open-channel block causing the decrease in the current amplitude.
KW - Anesthetics
KW - Channel block
KW - Computer simulations
KW - Isoflurane
KW - Patch-clamp
KW - γ-Aminobutyric acid (A) receptor
UR - http://www.scopus.com/inward/record.url?scp=0035854615&partnerID=8YFLogxK
U2 - 10.1016/S0304-3940(01)01950-4
DO - 10.1016/S0304-3940(01)01950-4
M3 - Article
C2 - 11427309
AN - SCOPUS:0035854615
SN - 0304-3940
VL - 307
SP - 97
EP - 100
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -