Premium
GABAergic mIPSCs in rat cerebellar Purkinje cells are modulated by TrkB and mGluR1‐mediated stimulation of Src
Author(s) -
Boxall Andrew R.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00677.x
Subject(s) - tropomyosin receptor kinase b , gabaa receptor , brain derived neurotrophic factor , chemistry , neuroscience , proto oncogene tyrosine protein kinase src , gabaergic , metabotropic glutamate receptor 1 , microbiology and biotechnology , neurotrophic factors , biology , receptor , glutamate receptor , metabotropic glutamate receptor , signal transduction , inhibitory postsynaptic potential , biochemistry
1 Whilst protein tyrosine kinase (PTK) activity can modulate expressed GABA A receptors in cell culture, the physiological consequences on synaptic GABA A receptors are unknown. This was examined using whole‐cell recording of bicuculline‐sensitive mIPSCs in Purkinje cells (PCs) in cerebellar slices. 2 Postsynaptic application of a peptide activator of the non‐receptor PTK Src (Src‐peptide) enhanced mIPSC amplitudes by 39 % in the presence of brain‐derived neurotrophic factor (BDNF) only; neurotrophin‐3 (NT‐3) was ineffective in this regard. Thus Src and TrkB (the receptor for BDNF) can physiologically interact to modulate synaptic GABA A receptors. 3 In the presence of BDNF, pharmacological activation of metabotrophic glutamate receptor subtype 1 (mGluR1) by ( S)‐ 3,5‐dihydrophenylglycine (3,5‐DHPG) also lead to a 32 % enhancement of mIPSCs. This enhancement was blocked by intracellular dialysis of PCs with PP1, a selective inhibitor of Src. 4 It is concluded that, whilst GABA A receptors are not constitutively regulated by endogenous PTK activity in PCs, co‐activation of TrkB by BDNF and Src by mGluR1 is required to modulate GABAergic synapses in PCs.