TY - JOUR
T1 - GABAA receptor activation and open-channel block by volatile anaesthetics
T2 - A new principle of receptor modulation?
AU - Haseneder, Rainer
AU - Rammes, Gerhard
AU - Zieglgänsberger, Walter
AU - Kochs, Eberhard
AU - Hapfelmeier, Gerhard
PY - 2002/9/6
Y1 - 2002/9/6
N2 - The rapid application of solutions containing the volatile anaesthetics isoflurane or sevoflurane induced inward currents in human embryonic kidney (HEK293) cells carrying rat recombinant α1β2γ2L GABAA receptor assemblies. The responses evoked by the anaesthetics applied via a fast delivery system were recorded using the patch-clamp technique in the whole-cell mode. The anaesthetics induced a fast inward current which was followed by a prominent tail current upon the rapid withdrawal of the agent. These currents were simulated using a kinetic scheme embodying two agonist-like binding steps required for receptor activation, and one binding step by which the anaesthetic induces an open-channel block. According to this model of a biphasic receptor modulation, the open-channel block delays the ion flux through the ligand-gated receptors and, thus, prolongs the overall duration of the current response. Open-channel blocks might also be operative in other ligand-gated ion channels to modulate synaptic strength.
AB - The rapid application of solutions containing the volatile anaesthetics isoflurane or sevoflurane induced inward currents in human embryonic kidney (HEK293) cells carrying rat recombinant α1β2γ2L GABAA receptor assemblies. The responses evoked by the anaesthetics applied via a fast delivery system were recorded using the patch-clamp technique in the whole-cell mode. The anaesthetics induced a fast inward current which was followed by a prominent tail current upon the rapid withdrawal of the agent. These currents were simulated using a kinetic scheme embodying two agonist-like binding steps required for receptor activation, and one binding step by which the anaesthetic induces an open-channel block. According to this model of a biphasic receptor modulation, the open-channel block delays the ion flux through the ligand-gated receptors and, thus, prolongs the overall duration of the current response. Open-channel blocks might also be operative in other ligand-gated ion channels to modulate synaptic strength.
KW - GABA receptor
KW - Isoflurane
KW - Kinetic modelling
KW - Open-channel block
KW - Patch-clamp
UR - http://www.scopus.com/inward/record.url?scp=0037031536&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(02)02194-5
DO - 10.1016/S0014-2999(02)02194-5
M3 - Article
C2 - 12223227
AN - SCOPUS:0037031536
SN - 0014-2999
VL - 451
SP - 43
EP - 50
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -