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  • 1
    It has been demonstrated that the regulation of recombinant GABAA receptors by phosphorylation depends on the subunit composition. Here we studied the regulation of synaptic GABAA 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 μm 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 μm).
  • 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 nm).
  • 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 (mIPSCFR) had a 10-90 % rise time of 410 ± 50 μs, an amplitude of 68 ± 6 pA, and a weighted decay time constant (τw) of 15.8 ± 2.9 ms. In contrast, slowly rising mIPSCs (mIPSCSR) displayed an approximately threefold slower rise time (1.15 ± 0.12 ms), 57 % smaller amplitude (29 ± 1.7 pA), but had a τw (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 GABAA receptors.