Isoflurane causes "flickering" of the acetylcholine receptor channel: observations using the patch clamp.
The authors investigated the effects of a volatile anesthetic (isoflurane) on the functional properties of a well characterized membrane ion channel (the acetylcholine receptor channel), using the patch clamp electrophysiological method together with local microperfusion of isoflurane. They found that isoflurane causes single acetylcholine receptor channels to "flicker" rapidly between open and closed states, reminiscent of the kinetic pattern induced by local anesthetics. The mean amplitude of currents flowing through open channels was unchanged. Although these observations initially suggested that isoflurane blocks open ion channels, closer analysis of the "isoflurane pattern" revealed features inconsistent with classical open channel block: the duration of bursts of channel openings is shortened, and that of the brief closures within bursts lengthens as the concentration of isoflurane is increased. The authors suggest that isoflurane exerts its characteristic effects on the kinetic properties of acetylcholine receptor channel by an allosteric mechanism. In addition, and apart from their mechanistic significance, these effects may underlie the known potentiation by isoflurane of curariform neuromuscular blockade.
Brett
R S
RS
Department of Anesthesiology, School of Medicine, SUNY, Stony Brook 11794-8480.
Dilger
J P
JP
Yland
K F
KF
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D004594:Electrophysiology / Q000379:methods; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009466:Neuromuscular Blocking Agents; D010477:Perfusion / Q000295:instrumentation; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D007473:Ion Channels; D009466:Neuromuscular Blocking Agents; D011950:Receptors, Cholinergic; D007530:Isoflurane; D000109:Acetylcholine