| Budget Amount *help |
¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Outline of Final Research Achievements |
We examined the sensitivity of Nav1.1-1.7 to TTX analogues provided by a collaborator and found that 1) chiriquitoxin (CHTX) exhibits low affinity to Nav1.7 due to steric repulsion against isoleucine residues in the TTX binding site, 2) contrary to previous reports, 4,9-anhydroTTX exhibits low affinity to Nav1.6, 3) the deoxy analogues exhibit low affinity to any Nav subtype.
We investigated the Nav inhibitory activity of various natural and non-natural TTX and STX derivatives provided by other collaborators and found that the one of the derivatives showed high affinity for Nav1.5, which is normally insensitive to TTX or STX.
We found arachidonic acid as an inhibitor of Nav expressed in mouse neuroblastoma Neuro 2A from the marine sponge Halichondria okadai, and investigated the details of the inhibition mechanism.
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