インスリンによる島皮質抑制性シナプス伝達増強に対するシナプス前細胞PKB / AKt経路の関与

• Published in: 日本薬理学会年会要旨集 p. 2-B-O04-2
• Main Authors: 小林, 真之, 北野, 晃平, 小林, 理美, 中谷, 有香
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2023
• Subjects: cerebral cortex; inhibitory postsynaptic potential (IPSP); patch clamp
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.97.0_2-B-O04-2

Insulin receptors are expressed in the cerebral cortex including the insular cortex (IC). However, little information is available for the mechanisms how insulin modulates neural activities in the cerebral cortex. Here, we examined effects of insulin on synaptic transmission between fast-spiking GABAergic neurons (FSNs) and pyramidal neurons (PyNs) in the IC using multiple whole-cell patch-clamp recording.We found that insulin increased the repetitive spike firing rate with a decrease in the threshold potential without changing the resting membrane potentials and input resistance of FSNs. The amplitude of unitary IPSCs (uIPSCs) was significantly increased and paired-pulse ratio of uIPSCs was significantly decreased by insulin. S961, an insulin receptor antagonist, and lavendustin A, a tyrosine kinase inhibitor, interrupted the effect of insulin on uIPSCs. In addition, wortmannin, a PI-3 kinase inhibitor, deguelin, a PKB/Akt inhibitor, and Akt inhibitor VIII significantly suppressed insulin-induced facilitation of uIPSCs. On the other hand, the effect of insulin was not blocked by PD98059, a MAPK inhibitor.These results suggest that insulin increased release of GABA from FSNs by activating PKB/Akt cascade.