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Differential regulation of synaptic GABA A receptors by cAMP‐dependent protein kinase in mouse cerebellar and olfactory bulb neurones
Author(s) -
Nusser Zoltan,
Sieghart Werner,
Mody Istvan
Publication year - 1999
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.1469-7793.1999.00421.x
Subject(s) - olfactory bulb , gabaa receptor , biology , inhibitory postsynaptic potential , protein subunit , biophysics , patch clamp , microbiology and biotechnology , protein kinase a , granule cell , receptor , kinase , neuroscience , chemistry , biochemistry , central nervous system , dentate gyrus , gene
1 It has been demonstrated that the regulation of recombinant GABA A receptors by phosphorylation depends on the subunit composition. Here we studied the regulation of synaptic GABA A receptor function by cAMP‐dependent protein kinase (PKA) in neurones expressing distinct receptor subtypes. 2 Light microscopic immunocytochemistry revealed that granule cells of the olfactory bulb express only the β3 as the β subunit variant, whereas cerebellar stellate and basket cells express only the β2 as the β subunit. 3 In cerebellar interneurones, intracellular application of 20 μ m microcystin, a protein phosphatase 1/2A inhibitor, prolonged (63 ± 14 %; mean ± s.e.m.s ) the decay time course of miniature IPSCs (mIPSCs) without significantly affecting their amplitude, rise time and frequency. The effect of microcystin could be blocked by co‐applying PKA inhibitory peptide (PKA‐I, 1 μ m ). 4 No significant changes in any of the mIPSC parameters could be detected after intracellular application of PKA‐I alone or following the inhibition of calcineurin with FK506 (50 n m ). 5 In granule cells of the olfactory bulb expressing the β3 subunit fast and slowly rising mIPSCs were detected, resulting in a bimodal distribution of the 10‐90 % rise times, suggesting two distinct populations of events. Fast rising mIPSCs (mIPSC FR ) had a 10‐90 % rise time of 410 ± 50 μs, an amplitude of 68 ± 6 pA, and a weighted decay time constant (τ w ) of 15.8 ± 2.9 ms. In contrast, slowly rising mIPSCs (mIPSC SR ) displayed an approximately threefold slower rise time (1.15 ± 0.12 ms), 57 % smaller amplitude (29 ± 1.7 pA), but had a τ w (16.8 ± 3.0 ms) similar to that of the fast events. 6 mIPSCs in olfactory granule cells were not affected by the intracellular perfusion of microcystin. In spite of this, intracellular administration of constitutively active PKA caused a small, gradual, but significant increase (18 ± 5 %) in the amplitude of the events without changing their time course. 7 These findings demonstrate a cell‐type‐dependent regulation of synaptic inhibition by protein phosphorylation. Furthermore, our results show that the effect of PKA‐mediated phosphorylation on synaptic inhibition depends upon the subunit composition of postsynaptic GABA A receptors.