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Biomedical subjects

R Chittajallu

Publications and source records attributed to R Chittajallu.

7 recordsLinked to original sources
PubMed2000

PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses.

We investigated the role of PDZ proteins (GRIP, ABP, and PICK1) interacting with the C-terminal GluR2 by infusing a ct-GluR2 peptide ("pep2-SVKI") into CA1 pyramidal neurons in hippocampal slices using whole-cell recordings. Pep2-SVKI, but not a control or PICK1 selective peptide, caused AMPAR-mediated EPSC amplitude to increase in approximately one-third of control neurons and in most neurons following the prior induction of LTD. Pep2-SVKI also blocked LTD; however, this occurred in all neurons. A PKC inhibitor prevented these effects of pep2-SVKI on synaptic transmission and LTD. We propose a model in which the maintenance of LTD involves the binding of AMPARs to PDZ proteins to prevent their reinsertion. We also present evidence that PKC regulates AMPAR reinsertion during dedepression.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Kainate receptors: subunits, synaptic localization and function.

Although it is well established that kainate receptors constitute an entirely separate group of proteins from AMPA receptors, their physiological functions remain unclear. The molecular cloning of subunits that form kainate receptors and the ability to study recombinant receptors is leading to an increased understanding of their functional properties. Furthermore, the development of kainate receptor-selective agonists and antagonists over the past few years is now allowing the physiological roles of these receptors and, in some cases, specific subunits to be investigated. As a consequence, the synaptic activation of postsynaptic kainate receptors and the presence of presynaptic kainate receptors that serve to regulate excitatory and inhibitory synaptic transmission have been described, and will be discussed in this article by Ramesh Chittajallu, Steven Braithwaite, Vernon Clarke and Jeremy Henley.

Animals↗
PubMed1999

Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction.

We investigated whether the interaction between the N-ethyl-maleimide-sensitive fusion protein (NSF) and the AMPA receptor (AMPAR) subunit GluR2 is involved in synaptic plasticity in the CA1 region of the hippocampus. Blockade of the NSF-GluR2 interaction by a specific peptide (pep2m) introduced into neurons prevented homosynaptic, de novo long-term depression (LTD). Moreover, saturation of LTD prevented the pep2m-induced reduction in AMPAR-mediated excitatory postsynaptic currents (EPSCs). Minimal stimulation experiments indicated that both pep2m action and LTD were due to changes in quantal size and quantal content but were not associated with changes in AMPAR single-channel conductance or EPSC kinetics. These results suggest that there is a pool of AMPARs dependent on the NSF-GluR2 interaction and that LTD expression involves the removal of these receptors from synapses.

Animals↗
PubMed1997

Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology.

BACKGROUND & AIMS: A less costly cancer surveillance method for Barrett's esophagus is desirable. The aim of this study was to compare nonendoscopic balloon cytology with biopsy and brush cytology for detecting dysplasia and carcinoma in patients with Barrett's esophagus. METHODS: Patients in a surveillance program underwent balloon cytology before endoscopy with biopsy and brush cytology. Results of cytology were compared with those of histology. RESULTS: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with biopsy. CONCLUSIONS: Balloon cytology detected 80% of patients with high-grade dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest that a more abrasive balloon may improve balloon cytology sensitivity. The potential cost savings of balloon cytology compared with endoscopic cancer surveillance in Barrett's esophagus support further studies of this technique.

Adenocarcinoma↗
PubMed1996

Regulation of glutamate release by presynaptic kainate receptors in the hippocampus.

Most reported actions of kainate are mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors. Here we report that, unlike AMPA which stimulates, kainate elicits a dose-dependent decrease in L-glutamate release from rat hippocampal synaptosomes and also depresses glutamatergic synaptic transmission. Brief exposure to kainate inhibited Ca(2+)-dependent [3H]L-glutamate release by up to 80%. Inhibition was reversed by kainate antagonists but not by the AMPA-selective non-competitive antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466). A corresponding reversible kainate-evoked depression of NMDA (N-methyl-D-aspartate) receptor-mediated excitatory postsynaptic currents (e.p.s.cs) was observed when AMPA receptors were blocked by GYKI 52466. The synaptic depression was preceded by a brief period of enhanced release and a small inward current was also observed. The effects of kainate were unaffected by metabotropic glutamate (mGlu), GABAA, GABAB, glycine and adenosine receptor antagonists. These results indicate that glutamate release can be modulated directly by kainate autoreceptors.

Animals↗
PubMedDate not supplied

Ca2+ and synaptic plasticity.

A major effort in neuroscience is directed towards understanding the roles of Ca2+ signalling in the induction of synaptic plasticity. Here, we summarize the evidence concerning Ca2+ signalling, paying particular attention to CA1 excitatory synapses, and its relationship to the induction of long-term potentiation and long-term depression. We discuss the ways in which synaptic activation can elevate Ca2+ postsynaptically and how dendritic spines may act as a Ca2+ compartment which can both isolate and integrate Ca2+ signals.

Animals↗