NR2 subunit-dependence of NMDA receptor channel block by external Mg2
The vital roles played by NMDA receptors in CNS physiology depend critically on powerful voltage-dependent channel block by external Mg 2+ (Mg 2+ o ). NMDA receptor channel block by Mg 2+ o depends on receptor subunit composition: NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR...
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| Veröffentlicht in: | The Journal of physiology 2005-01, Vol.562 (2), p.319-331 |
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| creator | Qian, Anqi Buller, Amy L. Johnson, Jon W. |
| description | The vital roles played by NMDA receptors in CNS physiology depend critically on powerful voltage-dependent channel block by
external Mg 2+ (Mg 2+ o ). NMDA receptor channel block by Mg 2+ o depends on receptor subunit composition: NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR1/2B receptors
are more strongly inhibited by Mg 2+ o than are NR1/2C or NR1/2D receptors. We investigated the effects of Mg 2+ o on single-channel and whole-cell currents recorded from recombinant NR1/2D and NR1/2A receptors expressed in HEK293 and 293T
cells. The main conclusions are as follows: (1) Voltage-dependent inhibition by Mg 2+ o of whole-cell NR1/2D receptor responses was at least 4-fold weaker than inhibition of NR1/2A receptor responses at all voltages
tested. (2) Channel block by Mg 2+ o reduced the duration of NR1/2D receptor single-channel openings; this reduction was used to estimate the apparent blocking
rate of Mg 2+ o ( k +,app ). The k +,app for NR1/2D receptors was similar to but moderately slower than the k +,app obtained from cortical NMDA receptors composed of NR1, NR2A and NR2B subunits at all voltages tested. (3) Mg 2+ o blocking events induced an additional component in the closed-duration distribution; this component was used to estimate
the apparent unblocking rate of Mg 2+ o ( k â,app ). The k â,app for NR1/2D receptors was much faster than the k â,app for cortical receptors at all voltages tested. The voltage-dependence of the k â,app of NR1/2D and cortical receptors differed in a manner that suggested that Mg 2+ o may permeate NR1/2D receptors more easily than cortical receptors. (4) Mg 2+ o inhibits NR1/2D receptors less effectively than cortical receptors chiefly because Mg 2+ o unbinds much more rapidly from NR1/2D receptors. |
| doi_str_mv | 10.1113/jphysiol.2004.076737 |
| format | Article |
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external Mg 2+ (Mg 2+ o ). NMDA receptor channel block by Mg 2+ o depends on receptor subunit composition: NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR1/2B receptors
are more strongly inhibited by Mg 2+ o than are NR1/2C or NR1/2D receptors. We investigated the effects of Mg 2+ o on single-channel and whole-cell currents recorded from recombinant NR1/2D and NR1/2A receptors expressed in HEK293 and 293T
cells. The main conclusions are as follows: (1) Voltage-dependent inhibition by Mg 2+ o of whole-cell NR1/2D receptor responses was at least 4-fold weaker than inhibition of NR1/2A receptor responses at all voltages
tested. (2) Channel block by Mg 2+ o reduced the duration of NR1/2D receptor single-channel openings; this reduction was used to estimate the apparent blocking
rate of Mg 2+ o ( k +,app ). The k +,app for NR1/2D receptors was similar to but moderately slower than the k +,app obtained from cortical NMDA receptors composed of NR1, NR2A and NR2B subunits at all voltages tested. (3) Mg 2+ o blocking events induced an additional component in the closed-duration distribution; this component was used to estimate
the apparent unblocking rate of Mg 2+ o ( k â,app ). The k â,app for NR1/2D receptors was much faster than the k â,app for cortical receptors at all voltages tested. The voltage-dependence of the k â,app of NR1/2D and cortical receptors differed in a manner that suggested that Mg 2+ o may permeate NR1/2D receptors more easily than cortical receptors. (4) Mg 2+ o inhibits NR1/2D receptors less effectively than cortical receptors chiefly because Mg 2+ o unbinds much more rapidly from NR1/2D receptors.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/jphysiol.2004.076737</identifier><identifier>PMID: 15513936</identifier><language>eng</language><publisher>9600 Garsington Road , Oxford , OX4 2DQ , UK: The Physiological Society</publisher><subject>Algorithms ; Animals ; Cell Line ; Cerebral Cortex - drug effects ; Cerebral Cortex - metabolism ; Electric Stimulation ; Electrophysiology ; Excitatory Amino Acid Antagonists ; Humans ; Kinetics ; Magnesium - pharmacology ; Membrane Potentials - physiology ; Molecular and Genomic Physiology ; Patch-Clamp Techniques ; Rats ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Solutions ; Transfection</subject><ispartof>The Journal of physiology, 2005-01, Vol.562 (2), p.319-331</ispartof><rights>2005 The Journal of Physiology © 2005 The Physiological Society</rights><rights>The Physiological Society 2005 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665508/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665508/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,1412,1428,27905,27906,45555,45556,46390,46814,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15513936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qian, Anqi</creatorcontrib><creatorcontrib>Buller, Amy L.</creatorcontrib><creatorcontrib>Johnson, Jon W.</creatorcontrib><title>NR2 subunit-dependence of NMDA receptor channel block by external Mg2</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>The vital roles played by NMDA receptors in CNS physiology depend critically on powerful voltage-dependent channel block by
external Mg 2+ (Mg 2+ o ). NMDA receptor channel block by Mg 2+ o depends on receptor subunit composition: NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR1/2B receptors
are more strongly inhibited by Mg 2+ o than are NR1/2C or NR1/2D receptors. We investigated the effects of Mg 2+ o on single-channel and whole-cell currents recorded from recombinant NR1/2D and NR1/2A receptors expressed in HEK293 and 293T
cells. The main conclusions are as follows: (1) Voltage-dependent inhibition by Mg 2+ o of whole-cell NR1/2D receptor responses was at least 4-fold weaker than inhibition of NR1/2A receptor responses at all voltages
tested. (2) Channel block by Mg 2+ o reduced the duration of NR1/2D receptor single-channel openings; this reduction was used to estimate the apparent blocking
rate of Mg 2+ o ( k +,app ). The k +,app for NR1/2D receptors was similar to but moderately slower than the k +,app obtained from cortical NMDA receptors composed of NR1, NR2A and NR2B subunits at all voltages tested. (3) Mg 2+ o blocking events induced an additional component in the closed-duration distribution; this component was used to estimate
the apparent unblocking rate of Mg 2+ o ( k â,app ). The k â,app for NR1/2D receptors was much faster than the k â,app for cortical receptors at all voltages tested. The voltage-dependence of the k â,app of NR1/2D and cortical receptors differed in a manner that suggested that Mg 2+ o may permeate NR1/2D receptors more easily than cortical receptors. (4) Mg 2+ o inhibits NR1/2D receptors less effectively than cortical receptors chiefly because Mg 2+ o unbinds much more rapidly from NR1/2D receptors.</description><subject>Algorithms</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - metabolism</subject><subject>Electric Stimulation</subject><subject>Electrophysiology</subject><subject>Excitatory Amino Acid Antagonists</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Magnesium - pharmacology</subject><subject>Membrane Potentials - physiology</subject><subject>Molecular and Genomic Physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Rats</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Solutions</subject><subject>Transfection</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtv1DAUhS0EotPCP0DIK7rK4MfYHm-QqtLyUFsQKmvLia8nLh47xElL_j0zSkvL6i7Od86R7kHoDSVLSil_f9O1Uwk5LhkhqyVRUnH1DC3oSupKKc2fowUhjFVcCXqADku5IYRyovVLdECFoFxzuUBnVz8YLmM9pjBUDjpIDlIDOHt8dfnxBPfQQDfkHjetTQkirmNufuF6wvBngD7ZiC837BV64W0s8Pr-HqGf52fXp5-ri2-fvpyeXFQt45JWUnrBlfUUYO2dr0E6Ky2nVq-JBC5W4CSjEsiKeK-9c0TVQisuHFcg5JofoQ9zbjfWW3ANpKG30XR92Np-MtkG87-SQms2-dZQKYUg-4B39wF9_j1CGcw2lAZitAnyWMz-iUxqvQPfPm36V_HwuR2wnoG7EGF61InZr2Me1jH7dcy8jrn--l1yurMez9Y2bNq70IOZ4ZKbAMNkhGSGGU41_wt73pLD</recordid><startdate>20050115</startdate><enddate>20050115</enddate><creator>Qian, Anqi</creator><creator>Buller, Amy L.</creator><creator>Johnson, Jon W.</creator><general>The Physiological Society</general><general>Blackwell Science Ltd</general><general>Blackwell Science Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050115</creationdate><title>NR2 subunit-dependence of NMDA receptor channel block by external Mg2</title><author>Qian, Anqi ; Buller, Amy L. ; Johnson, Jon W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h2361-66f537af1ee8fdfbe6da6a31a9806e354ed6216e040ff9fdd07b59735d37e5683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Algorithms</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - metabolism</topic><topic>Electric Stimulation</topic><topic>Electrophysiology</topic><topic>Excitatory Amino Acid Antagonists</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Magnesium - pharmacology</topic><topic>Membrane Potentials - physiology</topic><topic>Molecular and Genomic Physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Rats</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Solutions</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qian, Anqi</creatorcontrib><creatorcontrib>Buller, Amy L.</creatorcontrib><creatorcontrib>Johnson, Jon W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qian, Anqi</au><au>Buller, Amy L.</au><au>Johnson, Jon W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NR2 subunit-dependence of NMDA receptor channel block by external Mg2</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2005-01-15</date><risdate>2005</risdate><volume>562</volume><issue>2</issue><spage>319</spage><epage>331</epage><pages>319-331</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>The vital roles played by NMDA receptors in CNS physiology depend critically on powerful voltage-dependent channel block by
external Mg 2+ (Mg 2+ o ). NMDA receptor channel block by Mg 2+ o depends on receptor subunit composition: NR1/2A receptors (receptors composed of NR1 and NR2A subunits) and NR1/2B receptors
are more strongly inhibited by Mg 2+ o than are NR1/2C or NR1/2D receptors. We investigated the effects of Mg 2+ o on single-channel and whole-cell currents recorded from recombinant NR1/2D and NR1/2A receptors expressed in HEK293 and 293T
cells. The main conclusions are as follows: (1) Voltage-dependent inhibition by Mg 2+ o of whole-cell NR1/2D receptor responses was at least 4-fold weaker than inhibition of NR1/2A receptor responses at all voltages
tested. (2) Channel block by Mg 2+ o reduced the duration of NR1/2D receptor single-channel openings; this reduction was used to estimate the apparent blocking
rate of Mg 2+ o ( k +,app ). The k +,app for NR1/2D receptors was similar to but moderately slower than the k +,app obtained from cortical NMDA receptors composed of NR1, NR2A and NR2B subunits at all voltages tested. (3) Mg 2+ o blocking events induced an additional component in the closed-duration distribution; this component was used to estimate
the apparent unblocking rate of Mg 2+ o ( k â,app ). The k â,app for NR1/2D receptors was much faster than the k â,app for cortical receptors at all voltages tested. The voltage-dependence of the k â,app of NR1/2D and cortical receptors differed in a manner that suggested that Mg 2+ o may permeate NR1/2D receptors more easily than cortical receptors. (4) Mg 2+ o inhibits NR1/2D receptors less effectively than cortical receptors chiefly because Mg 2+ o unbinds much more rapidly from NR1/2D receptors.</abstract><cop>9600 Garsington Road , Oxford , OX4 2DQ , UK</cop><pub>The Physiological Society</pub><pmid>15513936</pmid><doi>10.1113/jphysiol.2004.076737</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Algorithms Animals Cell Line Cerebral Cortex - drug effects Cerebral Cortex - metabolism Electric Stimulation Electrophysiology Excitatory Amino Acid Antagonists Humans Kinetics Magnesium - pharmacology Membrane Potentials - physiology Molecular and Genomic Physiology Patch-Clamp Techniques Rats Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Solutions Transfection |
| title | NR2 subunit-dependence of NMDA receptor channel block by external Mg2 |
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