{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:11:14Z","timestamp":1790626274101,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2003,3]]},"abstract":"<jats:p>We hypothesize that phosphorylation of AMPA receptors or associated synaptic proteins modulates the excitability of respiratory neurons in the preB\u00f6tzinger Complex (preB\u00f6tC), affecting respiratory rhythm. Using neonatal rat medullary slices that spontaneously generate respiratory rhythm, we examined the role of the cAMP\u2013PKA pathway (PKA:cAMP\u2010dependent protein kinase) in modulating glutamatergic synaptic transmission, the excitability of inspiratory neurons in the preB\u00f6tC and respiratory rhythm. Microinjection of forskolin, an activator of adenylate cyclase, into the preB\u00f6tC with or without the phosphodiesterase inhibitor 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX), decreased the period (increased the frequency) of respiratory\u2010related rhythmic motor output in the hypoglossal nerve (XIIn) to 84 % (without IBMX) and to 72% (with IBMX) of the pre\u2010injection baseline. In the presence of MK\u2010801, a non\u2010competitive NMDA receptor antagonist, microinjection of forskolin plus IBMX decreased the period to 66% of baseline levels. Microinjection of Rp\u2010adenosine 3\u2032,5\u2032\u2010cyclic monophosphothioate (Rp\u2010cAMPS), a PKA inhibitor, increased the period to 145% of baseline levels. Concurrent microinjection of Rp\u2010cAMPS and forskolin had no effect on the period. Bath application of 7\u03b2\u2010deacetyl\u20107\u03b2\u2010[\u03b3\u2010(morpholino)butyryl]\u2010forskolin hydrochloride (7Db\u2010forskolin, a water\u2010soluble derivative of forskolin): (1) decreased the period to 67% of baseline levels without affecting the amplitude of integrated XIIn inspiratory discharge, (2) induced a tonic inward current of 29 pA and enhanced inspiratory drive current (the amplitude increased to 183% and the integral increased to 184% of baseline) in voltage\u2010clamped (holding potential =\u221260 mV) preB\u00f6tC inspiratory neurons and (3) increased the frequency to 195 % and amplitude to 118% of spontaneous excitatory postsynaptic currents (sEPSCs) during expiratory periods. Dideoxy\u2010forskolin did not have these effects. Intracellular perfusion with the catalytic subunit of PKA (cPKA) into preB\u00f6tC inspiratory neurons progressively enhanced inspiratory drive currents and, in the presence of TTX, increased the inward currents induced by local ejection of AMPA; the latter currents were blocked by 1,2,3,4\u2010tetrahydro\u20106\u2010nitro\u20102,3\u2010dioxo\u2010benzo[f]quinoxaline\u20107\u2010sulphonamide (NBQX, an AMPA\/kainate receptor antagonist). The effects of cPKA were blocked by co\u2010application of PKA inhibitor (6\u201322) amide (PKI). These results suggest that phosphorylation of postsynaptic AMPA receptors through the cAMP\u2013PKA pathway modulates both tonic and phasic excitatory amino acid synaptic transmission and excitability of inspiratory neurons in the preB\u00f6tC and, therefore, regulates respiratory rhythm. Moreover, the basal level of endogenous PKA activity appears to be a determinant of resting respiratory frequency.<\/jats:p>","DOI":"10.1113\/jphysiol.2002.031005","type":"journal-article","created":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:25:02Z","timestamp":1046478302000},"page":"543-553","source":"Crossref","is-referenced-by-count":44,"title":["Modulation of AMPA receptors by cAMP\u2010dependent protein kinase in PreB\u00f6tzinger complex inspiratory neurons regulates respiratory rhythm in the rat"],"prefix":"10.1113","volume":"547","author":[{"given":"Xuesi M.","family":"Shao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack 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