title: Vascular endothelial growth factor modulates voltage-gated Na(+) channel properties and depresses action potential firing in cultured rat hippocampal neurons.
abstract: Vascular endothelial growth factor (VEGF), an angiogenic factor, was found to modulate synaptic plasticity by affecting K(+) and Ca(2+) channels and protect neuron from death by depressing glutamatergic transmission. However, whether VEGF also modulates neuronal activity through modulating voltage-gated Na(+) channels (VGSCs), a main determinant of neuronal excitability, we observed the effects of VEGF on Na(+) channel properties and function on cultured rat hippocampal neurons through whole-cell patch-clamp recording. We found that VEGF decreased the Na(+) channel excitability by shifting the voltage-dependence of steady-state inactivation to more hyperpolarized direction, and increasing the time constants of recovery from inactivation without significantly affecting the activation process. The effect of VEGF on Na(+) channel steady-state inactivation was inhibited by the specific VEGF Flk-1 receptor antagonist SU1498, but was not affected by protein kinase C (PKC)-activator 1-oleoyl-2-acetyl-sn-glycerol (OAG). Furthermore, the inhibition of Na(+) currents by VEGF was frequency-dependent. In addition, the frequency of neuron firing evoked by current injection was reversibly depressed by VEGF. Therefore, our results suggest a potential role of VGSCs in the modulation of VEGF on neuronal excitability.
authors: Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, 801 He-Qing Rd., Shanghai 200240, PR China. sunguangchun@5thhospital.com
authors: Guang-chun
authors: GC
authors: Sun
authors: Yuan-yuan
authors: YY
authors: Ma
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D061566:Voltage-Gated Sodium Channels