title: VEGF attenuated increase of outward delayed-rectifier potassium currents in hippocampal neurons induced by focal ischemia via PI3-K pathway.
abstract: We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway.
authors: Institute of Biomedical Sciences and Department of Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Research Center on Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors: K W
authors: KW
authors: Wu
authors: Research Center on Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, PR China.
authors: P
authors: P
authors: Yang
authors: Research Center on Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, PR China.
authors: S S
authors: SS
authors: Li
authors: Research Center on Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, PR China.
authors: C W
authors: CW
authors: Liu
authors: Institute of Biomedical Sciences and Department of Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Research Center on Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, PR China. Electronic address: fysun@shmu.edu.cn.
authors: F Y
authors: FY
authors: Sun
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002544:Cerebral Infarction / Q000209:etiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D051663:Kv1.2 Potassium Channel / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D051663:Kv1.2 Potassium Channel; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D042461:Vascular Endothelial Growth Factor A; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D019869:Phosphatidylinositol 3-Kinases
keywords: hippocampal slice; middle cerebral artery occlusion; patch clamp; potassium channel; stroke; vascular endothelial growth factor