title: AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats following esophageal acid exposure.
abstract: 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.
  
  
  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
  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.
authors.affiliation: Division of Gastroenterology & Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: B
authors.initials: B
authors.lastname: Banerjee
authors.forename: B K
authors.initials: BK
authors.lastname: Medda
authors.forename: S
authors.initials: S
authors.lastname: Pochiraju
authors.forename: P
authors.initials: P
authors.lastname: Kannampalli
authors.forename: I M
authors.initials: IM
authors.lastname: Lang
authors.forename: J N
authors.initials: JN
authors.lastname: Sengupta
authors.forename: R
authors.initials: R
authors.lastname: Shaker
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004947:Esophagus / Q000187:drug effects; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006851:Hydrochloric Acid / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D006851:Hydrochloric Acid; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; C501449:Dlg4 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptor subunits; CaMKII; GluA1; anterior cingulate cortex (ACC); midcingulate cortex (MCC); postsynaptic densities (PSDs)