AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats following esophageal acid exposure. Neurogastroenterol Motil 2013 Dec;25(12):973-e776
Date
10/15/2013Pubmed ID
24118589Pubmed Central ID
PMC4097166DOI
10.1111/nmo.12233Scopus ID
2-s2.0-84888063018 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
BACKGROUND: We recently reported an increase in N-methyl-d-aspartate (NMDA) receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the rostral cingulate cortical (rCC) neurons following esophageal acid exposure in rats. As α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate the fast excitatory transmission and play a critical role in synaptic plasticity, in this study, we investigated the effect of esophageal acid exposure in rats on the expression of AMPA receptor subunits and the involvement of these molecular alterations in acid-induced sensitization of neurons in the anterior cingulate (ACC) and midcingulate (MCC) cortices.
METHODS: In molecular study, we examined GluA1 and GluA2 expression and phosphorylation in membrane preparations and in the isolated postsynaptic densities (PSDs) from rats receiving acute esophageal exposure of either saline (control group) or 0.1 N HCl (experimental group). In electrophysiological study, the effect of selective AMPA receptor (Ca(2+) permeable) antagonist IEM-1460 and CaMKII inhibitor KN-93 was tested on responses of cortical neurons during acid infusion to address the underlying molecular mechanism of acid-induced sensitization.
KEY RESULTS: The acid exposure significantly increased expression of GluA1, pGluA1Ser(831) , and phosphorylated CaMKIIThr(286) , in the cortical membrane preparations. In isolated PSDs, a significant increase in pGluA1Ser(831) was observed in acid-treated rats compared with controls. Microinjection of IEM-1460 or KN-93 near the recording site significantly attenuated acid-induced sensitization of cortical neurons.
CONCLUSIONS & INFERENCES: The underlying mechanism of acid-induced cortical sensitization involves upregulation and CaMKII-mediated phosphorylation of GluA1. These molecular changes of AMPA receptors subunit GluA1 in the cortical neurons might play an important role in acid-induced esophageal hypersensitivity.
Author List
Banerjee B, Medda BK, Pochiraju S, Kannampalli P, Lang IM, Sengupta JN, Shaker RAuthors
Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of WisconsinIvan M. Lang DVM, PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Bidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2
Disks Large Homolog 4 Protein
Esophagus
Gyrus Cinguli
Hydrochloric Acid
Intracellular Signaling Peptides and Proteins
Male
Membrane Proteins
Neuronal Plasticity
Neurons
Phosphorylation
Rats
Rats, Sprague-Dawley
Receptors, AMPA
