A rapid increase in the total number of cell surface functional GABAA receptors induced by brain-derived neurotrophic factor in rat visual cortex.
The number of postsynaptic gamma-aminobutyric acid type A (GABAA) receptors is a fundamental determinant of the variability of inhibitory synaptic responses in the central nervous system. In rat visual cortex, [3H]SR-95531 binding assays revealed that brain-derived neurotrophic factor (BDNF), one of the neurotrophins, induced a rapid increase in the total number of cell surface GABAA receptors, through the activation of Trk B receptor tyrosine kinases. We also demonstrated that BDNF rapidly induced a sustained potentiation of GABAA receptor-mediated currents, using nystatin-perforated patch clamp recordings, in visual cortical layer 5 pyramidal neurons freshly isolated from P14 rats. The potentiation was caused by the activation of Trk B receptor tyrosine kinase and phospholipase C-gamma. In addition, intracellular Ca2+ was important for the potentiation of GABAA responses induced by BDNF. The selective increase in mean miniature inhibitory postsynaptic (mIPSC) current amplitude without effects on mIPSC time courses supports the idea that BDNF rapidly induces an increase in the total number of cell surface functional GABAA receptors in visual cortical pyramidal neurons. These results suggest that BDNF could alter the number of cell surface GABAA receptors in a region-specific manner.
Mizoguchi
Yoshito
Y
Cellular and Systems Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kanematsu
Takashi
T
Hirata
Masato
M
Nabekura
Junichi
J
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009761:Nystatin; D018408:Patch-Clamp Techniques; D051966:Phospholipase C gamma; D011724:Pyridazines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D014316:Tritium; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014793:Visual Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D011724:Pyridazines; D011963:Receptors, GABA-A; D014316:Tritium; D009761:Nystatin; C049853:gabazine; D020813:Receptor, trkB; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium