科研之友
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摘要
A kinase anchoring proteins (AKAPs) assemble cAMP dependent protein kinase (PI(A) into signaling complexes with a wide range of ion channels, including N-methyl-D-aspartate (NMDA)-subtype glutamate receptor (NMDAR) that is critical for the central sensitization of nociceptive behaviors. Although PICA has been widely described in the regulation of NMDAR-dependent nociceptive transmission and plasticity, the roles of AKAPs in these processes are largely unknown as yet. The present study interfered with AKAPs/PICA interaction by introducing stearated Ht31 peptide (St-Ht31) into spinal dorsal horn neurons, and investigated the possible changes of primary afferent-evoked, NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs). Whole-cell patch clamp recordings demonstrated that intracellular loading of St-Ht31 through the glass pipettes didn't affect NMDAR-mediated synaptic responses in the spinal cord slices from intact mice. When inflammatory pain was established by intraplantar injection of Complete Freund's Adjuvant (CFA), however, St-Ht31 significantly repressed the amplitudes of NMDAR-EPSCs by selectively removing GluN2B subunit-containing NMDAR out of synapses. With the inhibition of NMDAR-mediated nociceptive transmission, St-Ht31 effectively ameliorated CFA-induced inflammatory pain. Pharmacological manipulation of microtubule-based NMDAR transport, dynamin-dependent NMDAR endocytosis or actin depolymerization abolished the inhibitory effects of St-Ht31 peptide on NMDAR-EPSCs, suggesting that disruption of AKAPs/PICA interaction by St-Ht31 might disturb multiple NMDAR trafficking steps to reduce the receptor synaptic expression and spinal sensitization.
- 出版日期2015-2
- 单位兰州大学
