Molecular targets of volatile anesthetics isoflurane at the calyx of Held synapse.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16467
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• 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)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: Isoflurane / calyx of Held / capacitance measurement / exo-endocytosis / neurotransmission

Outline of Final Research Achievements

Synaptic mechanisms of general anesthesia remain unidentified. In rat brainstem slices, isoflurane inhibits excitatory transmitter release by blocking presynaptic calcium channels and exocytic machinery, with the latter mechanism predominating in its inhibitory effect on high-frequency transmission. Both in slice and in vivo, isoflurane preferentially inhibits spike transmission induced by high-frequency presynaptic inputs. This low-pass filtering action of isoflurane likely plays a significant role in general anesthesia.

Free Research Field

Anesthesiology

Academic Significance and Societal Importance of the Research Achievements

We discovered isoflurane preferentially inhibits high-frequency neurotransmission, therefore, selective inhibition by volatile anesthetics of high-frequency transmission will effectively attenuate such integral neuronal functions, with minimal inhibition of basal neuronal functions.