NR2 subunit‐dependence of NMDA receptor channel block by external Mg 2
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
−,app
). The
k
−,app
for NR1/2D receptors was much faster than the
k
−,app
for cortical receptors at all voltages tested. The voltage‐dependence of the
k
−,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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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
−,app
). The
k
−,app
for NR1/2D receptors was much faster than the
k
−,app
for cortical receptors at all voltages tested. The voltage‐dependence of the
k
−,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><language>eng</language><ispartof>The Journal of physiology, 2005-01, Vol.562 (2), p.319-331</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c967-2d8fa1429e4cdd5e5a1b371801b75850f7e6c2189571d83e1dfdef529b76074f3</citedby><cites>FETCH-LOGICAL-c967-2d8fa1429e4cdd5e5a1b371801b75850f7e6c2189571d83e1dfdef529b76074f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></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 Mg 2</title><title>The Journal of physiology</title><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
−,app
). The
k
−,app
for NR1/2D receptors was much faster than the
k
−,app
for cortical receptors at all voltages tested. The voltage‐dependence of the
k
−,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><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNo10E1OwzAQQGELgUQo3ICFL5DiseNMvKzKT5HaIqHuo8Qe05SQRHYq0R1H4IycBFWF1du9xcfYLYgpAKi73bA9xKZvp1KIbCowR4VnLIEsNymiUecsEULKVKGGS3YV404IUMKYhC3Wr5LHfb3vmvHn69vRQJ2jzhLvPV-v7mc8kKVh7AO326rrqOV129t3Xh84fY4Uuqrlqzcur9mFr9pIN3-dsM3jw2a-SJcvT8_z2TK1JsdUusJXkElDmXVOk66gVgiFgBp1oYVHyq2EwmgEVygC5x15LU2NucDMqwnLTlsb-hgD-XIIzUcVDiWI8ohR_mOUR4zyhKF-AVhPVSo</recordid><startdate>20050115</startdate><enddate>20050115</enddate><creator>Qian, Anqi</creator><creator>Buller, Amy L.</creator><creator>Johnson, Jon W.</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20050115</creationdate><title>NR2 subunit‐dependence of NMDA receptor channel block by external Mg 2</title><author>Qian, Anqi ; Buller, Amy L. ; Johnson, Jon W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c967-2d8fa1429e4cdd5e5a1b371801b75850f7e6c2189571d83e1dfdef529b76074f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qian, Anqi</creatorcontrib><creatorcontrib>Buller, Amy L.</creatorcontrib><creatorcontrib>Johnson, Jon W.</creatorcontrib><collection>CrossRef</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 Mg 2</atitle><jtitle>The Journal of physiology</jtitle><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
−,app
). The
k
−,app
for NR1/2D receptors was much faster than the
k
−,app
for cortical receptors at all voltages tested. The voltage‐dependence of the
k
−,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><doi>10.1113/jphysiol.2004.076737</doi><tpages>13</tpages></addata></record> |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete; Wiley Free Content; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| title | NR2 subunit‐dependence of NMDA receptor channel block by external Mg 2 |
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