Vascular endothelial growth factor inhibits outward delayed-rectifier potassium currents in acutely isolated hippocampal neurons

• Published in: Neuroscience 2003-04, Vol.118 (1), p.59-67
• Main Authors: XU, J. Y, ZHENG, P, SHEN, D. H, YANG, S. Z, ZHANG, L. M, HUANG, Y. L, SUN, F.-Y
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Biological and medical sciences; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells, Cultured; Central nervous system; Dose-Response Relationship, Drug; Electrophysiology; Endothelial Growth Factors - metabolism; Endothelial Growth Factors - pharmacology; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - metabolism; Intercellular Signaling Peptides and Proteins - pharmacology; Lymphokines - metabolism; Lymphokines - pharmacology; Male; Microscopy, Confocal; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons - drug effects; Neurons - metabolism; Potassium Channels - drug effects; Potassium Channels - metabolism; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1 - drug effects; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vascular Endothelial Growth Factor Receptor-2 - drug effects; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular Endothelial Growth Factors; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/s0306-4522(02)00948-x

In the present study, whole-cell patch-clamp recording was used to study whether vascular endothelial growth factor (VEGF) had a regulatory effect on the potassium-channel currents. The outward delayed-rectifier potassium currents (I(K)) were recorded in acutely isolated hippocampal neurons from 14-day-old rat brains. A local application of VEGF at the concentrations from 50 ng/ml to 200 ng/ml dose-dependently inhibited I(K). Administration of VEGF (100 ng/ml) to the neurons only for seconds could significantly reduce I(K) in 26 of 39 recorded cells. The currents could recover to 82.8+/-3.7% of the control level at 60 s after removing VEGF in the buffer. In the I-V curve analysis, VEGF negatively shifted the I-V curve of I(K); the inhibition was gradually enhanced as the membrane potential increased from -40 mV to 50 mV in 13 cells. Thus, the results reveal that VEGF inhibits I(K) in acute, reversible and voltage-dependent manners. Double staining combined with confocal laser scanning microscopy was used to simultaneously detect the distribution of VEGF receptors (flt-1 and flk-1) in the hippocampal section and isolated neuron. Results showed that flt-1-positive staining, but not flk-1, could be observed on the membrane of the hippocampal neuron in both preparations, suggesting the presence of neuronal membrane VEGF flt-1 receptors in the hippocampus. To investigate if the inhibition by VEGF on I(K) is related to the presence of flt-1 receptors, we further did flt-1-receptor immunostaining for the recorded neurons, which was labeled with Lucifer Yellow during the recording. Among nine recorded cells, five showing the inhibition by VEGF had detectable signals for flt-1 receptors on their membrane, whereas the other four showing no inhibition had no flt-1 receptors either. The results suggest that VEGF can acutely inhibit I(K) in the hippocampal neurons probably related to the presence of membrane flt-1 receptors in the neurons.