{"id":{"repo_id":"creighton","oai_identifier":"oai:cdr.creighton.edu:10504/7476"},"canonical_url":"https://search.dev.ndltd.org/etd/creighton/oai:cdr.creighton.edu:10504/7476","repository":{"repo_id":"creighton","name":"Creighton University","base_url":"https://cdr.creighton.edu/server/oai/request"},"display":{"title":"Effects of Ifenprodil on the Gating or NR1/2B NMDA Receptors","abstract":"The extracellular amino terminal domain (ATD) of the NR2 subunits differentially controls NMDA receptor activity. Ifenprodil binds to the ATD of NR1/NR2B receptors inhibiting the receptors. To delineate the effects of ifenprodil on NR1/NR2B receptor gating, we recorded steady state currents from cell attached and excised outside out patches at pH7.9. NR1/NR2B receptors were found to exhibit modal gating in both forms of recording which was unaffected by ifenprodil. Ifenprodil increased the occupancy of the receptor in long-lived shut conformations hence reducing the open probability of receptor with no change in the mean open time. We found a negative correlation between the open and shut intervals in NR1/NR2B recordings from cell attached patches containing one active channel similar to those previously reported for NR1/NR2A receptors. In order to further understand actions of ifenprodil we fitted the single channel data to previously proposed models for NMDA receptor gating. Log likelihood criteria suggested that a cyclic model containing two uncoupled open states (Schorge et al. 2005) fitted the data better compared to a linear model with sequential open states. Ifenprodil modified multiple gating steps when fitted to an `uncoupled cyclic' model and promoted receptor desensitization. In contrast a single gating step was modified when single channel data was fitted to the `linear' gating model. Our results suggest an allosteric cross talk between the NR1 and NR2 subunits of the NMDA receptors.","abstract_html":"The extracellular amino terminal domain (ATD) of the NR2 subunits differentially controls NMDA receptor activity. Ifenprodil binds to the ATD of NR1/NR2B receptors inhibiting the receptors. To delineate the effects of ifenprodil on NR1/NR2B receptor gating, we recorded steady state currents from cell attached and excised outside out patches at pH7.9. NR1/NR2B receptors were found to exhibit modal gating in both forms of recording which was unaffected by ifenprodil. Ifenprodil increased the occupancy of the receptor in long-lived shut conformations hence reducing the open probability of receptor with no change in the mean open time. We found a negative correlation between the open and shut intervals in NR1/NR2B recordings from cell attached patches containing one active channel similar to those previously reported for NR1/NR2A receptors. In order to further understand actions of ifenprodil we fitted the single channel data to previously proposed models for NMDA receptor gating. Log likelihood criteria suggested that a cyclic model containing two uncoupled open states (Schorge et al. 2005) fitted the data better compared to a linear model with sequential open states. Ifenprodil modified multiple gating steps when fitted to an `uncoupled cyclic' model and promoted receptor desensitization. In contrast a single gating step was modified when single channel data was fitted to the `linear' gating model. Our results suggest an allosteric cross talk between the NR1 and NR2 subunits of the NMDA receptors.","abstract_has_math":false,"creators":["Bhatt, Jay M."],"institution":"Creighton University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Dravid, Shashank M."],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-28","date_published":"2010-07-28","updated_at":"2026-07-24T01:51:41Z","subjects":[],"languages":["en_US"],"rights":["Copyright retained by Jay M. Bhatt"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10504/7476","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Dravid, Shashank M."]},{"key":"dc:creator","label":"Author","values":["Bhatt, Jay M."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-08-17T16:59:10Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2011-01-03T14:50:46Z"]},{"key":"dc:date.issued","label":"Date","values":["2010-07-28"]},{"key":"dc:publisher","label":"Institution","values":["Creighton University"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright retained by Jay M. Bhatt"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["Bhatt - thesis.pdf"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10504/7476"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The extracellular amino terminal domain (ATD) of the NR2 subunits differentially controls NMDA receptor activity. Ifenprodil binds to the ATD of NR1/NR2B receptors inhibiting the receptors. To delineate the effects of ifenprodil on NR1/NR2B receptor gating, we recorded steady state currents from cell attached and excised outside out patches at pH7.9. NR1/NR2B receptors were found to exhibit modal gating in both forms of recording which was unaffected by ifenprodil. Ifenprodil increased the occupancy of the receptor in long-lived shut conformations hence reducing the open probability of receptor with no change in the mean open time. We found a negative correlation between the open and shut intervals in NR1/NR2B recordings from cell attached patches containing one active channel similar to those previously reported for NR1/NR2A receptors. In order to further understand actions of ifenprodil we fitted the single channel data to previously proposed models for NMDA receptor gating. Log likelihood criteria suggested that a cyclic model containing two uncoupled open states (Schorge et al. 2005) fitted the data better compared to a linear model with sequential open states. Ifenprodil modified multiple gating steps when fitted to an `uncoupled cyclic' model and promoted receptor desensitization. In contrast a single gating step was modified when single channel data was fitted to the `linear' gating model. Our results suggest an allosteric cross talk between the NR1 and NR2 subunits of the NMDA receptors."]},{"key":"dc:title","label":"Title","values":["Effects of Ifenprodil on the Gating or NR1/2B NMDA Receptors"]}]}],"canonical_facts":{"dc:contributor.advisor":["Dravid, Shashank M."],"dc:creator":["Bhatt, Jay M."],"dc:date.accessioned":["2010-08-17T16:59:10Z"],"dc:date.available":["2011-01-03T14:50:46Z"],"dc:date.issued":["2010-07-28"],"dc:description.abstract":["The extracellular amino terminal domain (ATD) of the NR2 subunits differentially controls NMDA receptor activity. Ifenprodil binds to the ATD of NR1/NR2B receptors inhibiting the receptors. To delineate the effects of ifenprodil on NR1/NR2B receptor gating, we recorded steady state currents from cell attached and excised outside out patches at pH7.9. NR1/NR2B receptors were found to exhibit modal gating in both forms of recording which was unaffected by ifenprodil. Ifenprodil increased the occupancy of the receptor in long-lived shut conformations hence reducing the open probability of receptor with no change in the mean open time. We found a negative correlation between the open and shut intervals in NR1/NR2B recordings from cell attached patches containing one active channel similar to those previously reported for NR1/NR2A receptors. In order to further understand actions of ifenprodil we fitted the single channel data to previously proposed models for NMDA receptor gating. Log likelihood criteria suggested that a cyclic model containing two uncoupled open states (Schorge et al. 2005) fitted the data better compared to a linear model with sequential open states. Ifenprodil modified multiple gating steps when fitted to an `uncoupled cyclic' model and promoted receptor desensitization. In contrast a single gating step was modified when single channel data was fitted to the `linear' gating model. Our results suggest an allosteric cross talk between the NR1 and NR2 subunits of the NMDA receptors."],"dc:identifier.other":["Bhatt - thesis.pdf"],"dc:identifier.uri":["http://hdl.handle.net/10504/7476"],"dc:language.iso":["en_US"],"dc:publisher":["Creighton University"],"dc:rights":["Copyright retained by Jay M. Bhatt"],"dc:title":["Effects of Ifenprodil on the Gating or NR1/2B NMDA Receptors"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T01:51:41Z"}