title: Protein kinase A regulates the long-term potentiation of intrinsic excitability in neonatal trigeminal motoneurons.
abstract: Although much is known about neuronal plasticity in the mammalian hippocampus and other cortical neurons, the subcellular mechanisms underlying plasticity at the level of motor pools are less well characterized. Protein kinase A (PKA) activation plays an essential role in long-term potentiation of intrinsic excitability (LTP-IE) in layer V (LV) visual cortical neurons and may be involved in other systems as well. Trigeminal motoneurons (TMNs) participate in rhythmical motor behaviors, such as suckling, chewing, and swallowing. Using the whole-cell patch clamp method and various kinase inhibitors and activators, we investigated the mechanism of LTP-IE in neonatal rat TMNs. Ca(2+) depletion using ACSF with 0mM Ca(2+) or the Ca(2+) chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) blocked the long-lasting increase in intrinsic excitability in TMNs, showing that intracellular Ca(2+) during the induction protocol is necessary for the induction of LTP-IE. We next used specific inhibitors of PKA, protein kinase C, and calcium/calmodulin-dependent protein kinase II during the induction protocol. Only the PKA inhibitor H-89 blocked the increase in the firing rate induced by the induction protocol. In addition, forskolin, which activates PKA, induced a long-lasting increase in excitability that resembled the excitability produced by the induction protocol. Thus, we conclude that LTP-IE in TMNs is calcium-dependent, and PKA is the primary regulator of this process.
authors.affiliation: The first Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: sbshayan@dent.osaka-u.ac.jp.
authors.forename: Sanam
authors.initials: S
authors.lastname: Bakhshishayan
authors.forename: Akifumi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Tadataka
authors.initials: T
authors.lastname: Tsuji
authors.forename: Susumu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamanishi
authors.forename: Kohji
authors.initials: K
authors.lastname: Ishihama
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kogo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D009046:Motor Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014276:Trigeminal Nerve / Q000378:metabolism*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases
keywords: CaMKII; Long-term potentiation; PKA; PKC; Protein kinase A; TMNs; Trigeminal motoneuron; calcium/calmodulin-dependent protein kinase II; protein kinase A; protein kinase C; trigeminal motoneurons