Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms

Han Ying Wang, Kohgaku Eguchi, Takayuki Yamashita, Tomoyuki Takahashi

研究成果: Article査読

9 被引用数 (Scopus)

抄録

Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca21 currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca21 currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca21 influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.

本文言語English
ページ(範囲)4103-4115
ページ数13
ジャーナルJournal of Neuroscience
40
21
DOI
出版ステータスPublished - 20-05-2020
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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