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PKC and CaMK-II inhibitions coordinately rescue ischemia-induced GABAergic neuron dysfunction

2017; Impact Journals LLC; Volume: 8; Issue: 24 Linguagem: Inglês

10.18632/oncotarget.16947

1949-2553

Li Huang, Chun Wang, Shidi Zhao, Rongjing Ge, Sudong Guan, Jinhui Wang,

Receptor Mechanisms and Signaling

// Li Huang 1, * , Chun Wang 2, * , Shidi Zhao 1, * , Rongjing Ge 1 , Sudong Guan 1 and Jin-Hui Wang 1, 3 1 Department of Pathophysiology, Bengbu Medical College, Bengbu 233000, China 2 Department of Endocrinology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233040, China 3 Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China * These authors have contributed equally to this work Correspondence to: Jin-Hui Wang, email: jhw@ibp.ac.cn Keywords: ischemia, GABA, neuron, synapse, PKC and CaMK-II Received: February 17, 2017     Accepted: March 15, 2017     Published: April 07, 2017 ABSTRACT Cerebral ischemia leads to neuronal death for stroke, in which the imbalance between glutamatergic neurons and GABAergic neurons toward neural excitotoxicity is presumably involved. GABAergic neurons are vulnerable to pathological factors and impaired in an early stage of ischemia. The rescue of GABAergic neurons is expected to be the strategy to reserve ischemic neuronal impairment. As protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMK-II) are activated during ischemia, we have investigated whether the inhibitions of these kinases rescue the ischemic impairment of cortical GABAergic neurons. The functions of GABAergic neurons were analyzed by whole-cell recording in the cortical slices during ischemia and in presence of 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (CaMK-II inhibitor) and chelerythrine chloride (PKC inhibitor). Our results indicate that PKC inhibitor or CaMK-II inhibitor partially prevents ischemia-induced functional deficits of cortical GABAergic neurons. Moreover, the combination of PKC and CaMK-II inhibitors synergistically reverses this ischemia-induced deficit of GABAergic neurons. One of potential therapeutic strategies for ischemic stroke may be to rescue the ischemia-induced deficit of cortical GABAergic neurons by inhibiting PKC and CaMK-II.