Abstract:
BACKGROUND:It is well established that neuronal nicotinic acetylcholine receptors (nAChRs) are sensitive to inhalational anesthetics. The authors previously reported that halothane potently blocked alpha4beta2-type nAChRs of rat cortical neurons. However, the effect of isoflurane, which is widely used clinically, on nAChRs largely remains to be seen. The authors studied the effects of isoflurane as compared with sevoflurane and halothane on the human alpha4beta2 nAChRs expressed in human embryonic kidney cells. METHODS:The whole-cell and single-channel patch clamp techniques were used to record currents induced by acetylcholine. RESULTS:Isoflurane, sevoflurane, and halothane suppressed the acetylcholine-induced currents in a concentration-dependent manner with 50% inhibitory concentrations of 67.1, 183.3, and 39.8 microM, respectively, which correspond to 0.5 minimum alveolar concentration or less. When anesthetics were coapplied with acetylcholine, isoflurane and sevoflurane decreased the apparent affinity of receptor for acetylcholine, but halothane, in addition, decreased the maximum acetylcholine current. When isoflurane was preapplied and coapplied, its inhibitory action was independent of acetylcholine concentration. Isoflurane blocked the nAChR in both resting and activated states. Single-channel analyses revealed that isoflurane at 84 microM decreased the mean open time and burst duration without inducing "flickering" during channel openings. Isoflurane increased the mean closed time. As a result, the open probability of single channels was greatly reduced by isoflurane. CONCLUSIONS:Isoflurane, sevoflurane, and halothane potently blocked the alpha4beta2 nAChR. Isoflurane suppression of whole-cell acetylcholine currents was a result of decreases in the open time, burst duration, and open probability and an increase in the closed time of single channels. The high sensitivity of neuronal nAChRs to inhalational anesthetics is expected to play an important role in several stages of anesthesia.
journal_name
Anesthesiologyjournal_title
Anesthesiologyauthors
Yamashita M,Mori T,Nagata K,Yeh JZ,Narahashi Tdoi
10.1097/00000542-200501000-00015subject
Has Abstractpub_date
2005-01-01 00:00:00pages
76-84issue
1eissn
0003-3022issn
1528-1175pii
00000542-200501000-00015journal_volume
102pub_type
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