2019 Fiscal Year Annual Research Report
Molecular targets of volatile anesthetics isoflurane at the calyx of Held synapse.
| Project/Area Number |
18K16467
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
WANG Han・Ying 沖縄科学技術大学院大学, 細胞分子シナプス機能ユニット, 研究員 (70814333)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | Calyx of Held / Cerebral cortex / Isoflurane / Presynaptic reocrding / Capacitance / Action potential |
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| Outline of Annual Research Achievements |
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 excitatory post-synaptic currents by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending upon input frequencies. In simultaneous pre- 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 cortico-cortical 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.
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