A Single Residue Differentiates between Human Cardiac and Skeletal Muscle Na + Channel Slow Inactivation
Slow inactivation determines the availability of voltage-gated sodium channels during prolonged depolarization. Slow inactivation in hNa V1.4 channels occurs with a higher probability than hNa V1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using t...
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| Veröffentlicht in: | Biophysical journal 2001-05, Vol.80 (5), p.2221-2230 |
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| creator | Vilin, Yuriy Y. Fujimoto, Esther Ruben, Peter C. |
| description | Slow inactivation determines the availability of voltage-gated sodium channels during prolonged depolarization. Slow inactivation in hNa
V1.4 channels occurs with a higher probability than hNa
V1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using the macropatch technique we show that the DII S5-S6 p-region uniquely confers the probability of slow inactivation from parental hNa
V1.5 and hNa
V1.4 channels into chimerical constructs expressed in
Xenopus oocytes. Site-directed mutagenesis was used to test whether a specific region within DII S5-S6 controls the probability of slow inactivation. We found that substituting V754 in hNa
V1.4 with isoleucine from the corresponding position (891) in hNa
V1.5 produced steady-state slow inactivation statistically indistinguishable from that in wild-type hNa
V1.5 channels, whereas other mutations have little or no effect on slow inactivation. This result indicates that residues V754 in hNa
V1.4 and I891in hNa
V1.5 are unique in determining the probability of slow inactivation characteristic of these isoforms. Exchanging S5-S6 linkers between hNa
V1.4 and hNa
V1.5 channels had no consistent effect on the voltage-dependent slow time inactivation constants [
τ(V)]. This suggests that the molecular structures regulating rates of entry into and exit from the slow inactivated state are different from those controlling the steady-state probability and reside outside the p-regions. |
| doi_str_mv | 10.1016/S0006-3495(01)76195-4 |
| format | Article |
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V1.4 channels occurs with a higher probability than hNa
V1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using the macropatch technique we show that the DII S5-S6 p-region uniquely confers the probability of slow inactivation from parental hNa
V1.5 and hNa
V1.4 channels into chimerical constructs expressed in
Xenopus oocytes. Site-directed mutagenesis was used to test whether a specific region within DII S5-S6 controls the probability of slow inactivation. We found that substituting V754 in hNa
V1.4 with isoleucine from the corresponding position (891) in hNa
V1.5 produced steady-state slow inactivation statistically indistinguishable from that in wild-type hNa
V1.5 channels, whereas other mutations have little or no effect on slow inactivation. This result indicates that residues V754 in hNa
V1.4 and I891in hNa
V1.5 are unique in determining the probability of slow inactivation characteristic of these isoforms. Exchanging S5-S6 linkers between hNa
V1.4 and hNa
V1.5 channels had no consistent effect on the voltage-dependent slow time inactivation constants [
τ(V)]. This suggests that the molecular structures regulating rates of entry into and exit from the slow inactivated state are different from those controlling the steady-state probability and reside outside the p-regions.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1016/S0006-3495(01)76195-4</identifier><identifier>PMID: 11325725</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Electrophysiology ; Heart ; Humans ; Isoleucine - chemistry ; Kinetics ; Models, Biological ; Molecular biology ; Molecular Sequence Data ; Muscle, Skeletal - metabolism ; Muscular system ; Mutagenesis, Site-Directed ; Mutation ; Myocardium - metabolism ; Oocytes - metabolism ; Protein Isoforms ; Protein Structure, Tertiary ; Sodium ; Sodium Channels - chemistry ; Sodium Channels - genetics ; Valine - chemistry ; Xenopus</subject><ispartof>Biophysical journal, 2001-05, Vol.80 (5), p.2221-2230</ispartof><rights>2001 The Biophysical Society</rights><rights>Copyright Biophysical Society May 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-307ed25a411eb6912c8b0d6320dffeca7ec1f55b0fe7c6570d341917e787c43e3</citedby><cites>FETCH-LOGICAL-c490t-307ed25a411eb6912c8b0d6320dffeca7ec1f55b0fe7c6570d341917e787c43e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1301414/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-3495(01)76195-4$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3549,27923,27924,45994,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11325725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vilin, Yuriy Y.</creatorcontrib><creatorcontrib>Fujimoto, Esther</creatorcontrib><creatorcontrib>Ruben, Peter C.</creatorcontrib><title>A Single Residue Differentiates between Human Cardiac and Skeletal Muscle Na + Channel Slow Inactivation</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>Slow inactivation determines the availability of voltage-gated sodium channels during prolonged depolarization. Slow inactivation in hNa
V1.4 channels occurs with a higher probability than hNa
V1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using the macropatch technique we show that the DII S5-S6 p-region uniquely confers the probability of slow inactivation from parental hNa
V1.5 and hNa
V1.4 channels into chimerical constructs expressed in
Xenopus oocytes. Site-directed mutagenesis was used to test whether a specific region within DII S5-S6 controls the probability of slow inactivation. We found that substituting V754 in hNa
V1.4 with isoleucine from the corresponding position (891) in hNa
V1.5 produced steady-state slow inactivation statistically indistinguishable from that in wild-type hNa
V1.5 channels, whereas other mutations have little or no effect on slow inactivation. This result indicates that residues V754 in hNa
V1.4 and I891in hNa
V1.5 are unique in determining the probability of slow inactivation characteristic of these isoforms. Exchanging S5-S6 linkers between hNa
V1.4 and hNa
V1.5 channels had no consistent effect on the voltage-dependent slow time inactivation constants [
τ(V)]. This suggests that the molecular structures regulating rates of entry into and exit from the slow inactivated state are different from those controlling the steady-state probability and reside outside the p-regions.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Electrophysiology</subject><subject>Heart</subject><subject>Humans</subject><subject>Isoleucine - chemistry</subject><subject>Kinetics</subject><subject>Models, Biological</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscular system</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>Myocardium - metabolism</subject><subject>Oocytes - metabolism</subject><subject>Protein Isoforms</subject><subject>Protein Structure, Tertiary</subject><subject>Sodium</subject><subject>Sodium Channels - chemistry</subject><subject>Sodium Channels - 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Single Residue Differentiates between Human Cardiac and Skeletal Muscle Na + Channel Slow Inactivation</title><author>Vilin, Yuriy Y. ; Fujimoto, Esther ; Ruben, Peter C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-307ed25a411eb6912c8b0d6320dffeca7ec1f55b0fe7c6570d341917e787c43e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Electrophysiology</topic><topic>Heart</topic><topic>Humans</topic><topic>Isoleucine - chemistry</topic><topic>Kinetics</topic><topic>Models, Biological</topic><topic>Molecular biology</topic><topic>Molecular Sequence Data</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscular system</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation</topic><topic>Myocardium - metabolism</topic><topic>Oocytes - metabolism</topic><topic>Protein Isoforms</topic><topic>Protein 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China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vilin, Yuriy Y.</au><au>Fujimoto, Esther</au><au>Ruben, Peter C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Single Residue Differentiates between Human Cardiac and Skeletal Muscle Na + Channel Slow Inactivation</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2001-05-01</date><risdate>2001</risdate><volume>80</volume><issue>5</issue><spage>2221</spage><epage>2230</epage><pages>2221-2230</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>Slow inactivation determines the availability of voltage-gated sodium channels during prolonged depolarization. Slow inactivation in hNa
V1.4 channels occurs with a higher probability than hNa
V1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using the macropatch technique we show that the DII S5-S6 p-region uniquely confers the probability of slow inactivation from parental hNa
V1.5 and hNa
V1.4 channels into chimerical constructs expressed in
Xenopus oocytes. Site-directed mutagenesis was used to test whether a specific region within DII S5-S6 controls the probability of slow inactivation. We found that substituting V754 in hNa
V1.4 with isoleucine from the corresponding position (891) in hNa
V1.5 produced steady-state slow inactivation statistically indistinguishable from that in wild-type hNa
V1.5 channels, whereas other mutations have little or no effect on slow inactivation. This result indicates that residues V754 in hNa
V1.4 and I891in hNa
V1.5 are unique in determining the probability of slow inactivation characteristic of these isoforms. Exchanging S5-S6 linkers between hNa
V1.4 and hNa
V1.5 channels had no consistent effect on the voltage-dependent slow time inactivation constants [
τ(V)]. This suggests that the molecular structures regulating rates of entry into and exit from the slow inactivated state are different from those controlling the steady-state probability and reside outside the p-regions.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11325725</pmid><doi>10.1016/S0006-3495(01)76195-4</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present); PubMed Central |
| subjects | Amino Acid Sequence Animals Electrophysiology Heart Humans Isoleucine - chemistry Kinetics Models, Biological Molecular biology Molecular Sequence Data Muscle, Skeletal - metabolism Muscular system Mutagenesis, Site-Directed Mutation Myocardium - metabolism Oocytes - metabolism Protein Isoforms Protein Structure, Tertiary Sodium Sodium Channels - chemistry Sodium Channels - genetics Valine - chemistry Xenopus |
| title | A Single Residue Differentiates between Human Cardiac and Skeletal Muscle Na + Channel Slow Inactivation |
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