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Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats
Author(s) -
Banerjee B.,
Medda B. K.,
Zhang J.,
Tuchscherer V.,
Babygirija R.,
Kannampalli P.,
Sengupta J. N.,
Shaker R.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12834
Subject(s) - ampa receptor , downregulation and upregulation , glutamate receptor , dendritic spine , sensitization , receptor , neuroscience , synaptic plasticity , chemistry , long term depression , microbiology and biotechnology , medicine , endocrinology , hippocampal formation , biology , biochemistry , gene
Background We recently reported the involvement of AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex ( rCC ) as the underlying mechanism of acute esophageal acid‐induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre‐exposed to repeated esophageal acid exposures neonatally during neuronal development. Methods Two different esophageal acid exposure protocols in rats were used. Since AMPA receptor trafficking and channel conductance depend on Ca MKII α ‐mediated phosphorylation of AMPA receptor subunits, we examined the effect of esophageal acid on Ca MKII α activation and AMPA receptor expression in synaptoneurosomes and membrane preparations from rCC s. Key Results In cortical membrane preparations, GluA1 and pG luA1Ser 831 expression were significantly downregulated following prolonged acid exposures in adult rats; this was accompanied by the significant downregulation of cortical membrane pCaMKII α expression. No change in GluA1 and pG luA1Ser 831 expression was observed in rCC membrane preparations in rats pre‐exposed to acid neonatally followed by adult rechallenge. Conclusions & Inferences This study along with our previous findings suggests that synaptic AMPA receptor subunits expression and phosphorylation may be involved bidirectionally in both esophageal acid‐induced neuronal sensitization and acid‐dependent homeostatic plasticity in cortical neurons. The impairment of homeostatic compensatory mechanism as observed following early‐in‐life acid exposure could be the underlying mechanism of heightening cortical sensitization and esophageal hypersensitivity in patients with gastroesophageal reflux disease.