alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation
Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved i...
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Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2002-09, Vol.283 (3), p.C1001-C1008 |
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container_title | American Journal of Physiology: Cell Physiology |
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creator | Lyford, Greg L Strege, Peter R Shepard, Allan Ou, Yijun Ermilov, Leonid Miller, Steven M Gibbons, Simon J Rae, James L Szurszewski, Joseph H Farrugia, Gianrico |
description | Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the alpha(1C) L-type calcium channel subunit (Ca(V)1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a beta(2) calcium channel subunit in HEK-293 or Chinese hamster ovary cells. The heterologously expressed human cardiac alpha(1C) splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the alpha(1C) COOH terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming alpha(1C)-subunit. |
doi_str_mv | 10.1152/ajpcell.00140.2002 |
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The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the alpha(1C) L-type calcium channel subunit (Ca(V)1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a beta(2) calcium channel subunit in HEK-293 or Chinese hamster ovary cells. The heterologously expressed human cardiac alpha(1C) splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the alpha(1C) COOH terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming alpha(1C)-subunit.</description><identifier>ISSN: 0363-6143</identifier><identifier>DOI: 10.1152/ajpcell.00140.2002</identifier><identifier>PMID: 12176756</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Calcium Channels, L-Type - biosynthesis ; Calcium Channels, L-Type - drug effects ; Calcium Channels, L-Type - genetics ; Cell Line ; CHO Cells ; Cloning, Molecular ; Cricetinae ; Enzyme Inhibitors - pharmacology ; Humans ; Ion Channel Gating - drug effects ; Jejunum - metabolism ; Kidney - cytology ; Kidney - metabolism ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Molecular Sequence Data ; Organ Specificity - physiology ; Patch-Clamp Techniques ; Pressure ; Protein Isoforms - biosynthesis ; Protein Isoforms - drug effects ; Protein Isoforms - genetics ; Protein Structure, Tertiary - physiology ; Protein Subunits ; Sequence Deletion ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Space life sciences ; Stress, Mechanical ; Transfection</subject><ispartof>American Journal of Physiology: Cell Physiology, 2002-09, Vol.283 (3), p.C1001-C1008</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12176756$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lyford, Greg L</creatorcontrib><creatorcontrib>Strege, Peter R</creatorcontrib><creatorcontrib>Shepard, Allan</creatorcontrib><creatorcontrib>Ou, Yijun</creatorcontrib><creatorcontrib>Ermilov, Leonid</creatorcontrib><creatorcontrib>Miller, Steven M</creatorcontrib><creatorcontrib>Gibbons, Simon J</creatorcontrib><creatorcontrib>Rae, James L</creatorcontrib><creatorcontrib>Szurszewski, Joseph H</creatorcontrib><creatorcontrib>Farrugia, Gianrico</creatorcontrib><title>alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation</title><title>American Journal of Physiology: Cell Physiology</title><addtitle>Am J Physiol Cell Physiol</addtitle><description>Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the alpha(1C) L-type calcium channel subunit (Ca(V)1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a beta(2) calcium channel subunit in HEK-293 or Chinese hamster ovary cells. The heterologously expressed human cardiac alpha(1C) splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the alpha(1C) COOH terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming alpha(1C)-subunit.</description><subject>Animals</subject><subject>Calcium Channels, L-Type - biosynthesis</subject><subject>Calcium Channels, L-Type - drug effects</subject><subject>Calcium Channels, L-Type - genetics</subject><subject>Cell Line</subject><subject>CHO Cells</subject><subject>Cloning, Molecular</subject><subject>Cricetinae</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Ion Channel Gating - drug effects</subject><subject>Jejunum - metabolism</subject><subject>Kidney - cytology</subject><subject>Kidney - metabolism</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Molecular Sequence Data</subject><subject>Organ Specificity - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Pressure</subject><subject>Protein Isoforms - biosynthesis</subject><subject>Protein Isoforms - drug effects</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Structure, Tertiary - physiology</subject><subject>Protein Subunits</subject><subject>Sequence Deletion</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Space life sciences</subject><subject>Stress, Mechanical</subject><subject>Transfection</subject><issn>0363-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1Lw0AYhPeg2Fr9Ax4kJ2kPie-7m91NjhL8goIXFW_h7XZjt2w-zCZC_70tVjzNMDwMzDB2hZAgSn5L285Y7xMATCHhAPyETUEoEStMxYSdh7AFgJSr_IxNkKNWWqop-yDfbWiOxSKaFzR_X2DCF9EyHnadjQx548Y6MhtqGuuj2q4dDTbszSFqg22CG9z3P9nbz9HT4Nrmgp1W5IO9POqMvT3cvxZP8fLl8bm4W8YdinyINWSISgpAbiQSB6wqk2kJvALMuV3rNKUq05kxRkDOc5tpsJpWSki5TnMxYze_vV3ffo02DGXtwuEKamw7hlJjninguAevj-C42g8pu97V1O_Kvy_ED7GVXgY</recordid><startdate>200209</startdate><enddate>200209</enddate><creator>Lyford, Greg L</creator><creator>Strege, Peter R</creator><creator>Shepard, Allan</creator><creator>Ou, Yijun</creator><creator>Ermilov, Leonid</creator><creator>Miller, Steven M</creator><creator>Gibbons, Simon J</creator><creator>Rae, James L</creator><creator>Szurszewski, Joseph H</creator><creator>Farrugia, Gianrico</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200209</creationdate><title>alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation</title><author>Lyford, Greg L ; Strege, Peter R ; Shepard, Allan ; Ou, Yijun ; Ermilov, Leonid ; Miller, Steven M ; Gibbons, Simon J ; Rae, James L ; Szurszewski, Joseph H ; Farrugia, Gianrico</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p139t-70811653012c51a201ffc87502f0192ed744af878ccc30929e870e7ab6355d493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Calcium Channels, L-Type - biosynthesis</topic><topic>Calcium Channels, L-Type - drug effects</topic><topic>Calcium Channels, L-Type - genetics</topic><topic>Cell Line</topic><topic>CHO Cells</topic><topic>Cloning, Molecular</topic><topic>Cricetinae</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Ion Channel Gating - drug effects</topic><topic>Jejunum - metabolism</topic><topic>Kidney - cytology</topic><topic>Kidney - metabolism</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Molecular Sequence Data</topic><topic>Organ Specificity - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Pressure</topic><topic>Protein Isoforms - biosynthesis</topic><topic>Protein Isoforms - drug effects</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Structure, Tertiary - physiology</topic><topic>Protein Subunits</topic><topic>Sequence Deletion</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Space life sciences</topic><topic>Stress, Mechanical</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lyford, Greg L</creatorcontrib><creatorcontrib>Strege, Peter R</creatorcontrib><creatorcontrib>Shepard, Allan</creatorcontrib><creatorcontrib>Ou, Yijun</creatorcontrib><creatorcontrib>Ermilov, Leonid</creatorcontrib><creatorcontrib>Miller, Steven M</creatorcontrib><creatorcontrib>Gibbons, Simon J</creatorcontrib><creatorcontrib>Rae, James L</creatorcontrib><creatorcontrib>Szurszewski, Joseph H</creatorcontrib><creatorcontrib>Farrugia, Gianrico</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lyford, Greg L</au><au>Strege, Peter R</au><au>Shepard, Allan</au><au>Ou, Yijun</au><au>Ermilov, Leonid</au><au>Miller, Steven M</au><au>Gibbons, Simon J</au><au>Rae, James L</au><au>Szurszewski, Joseph H</au><au>Farrugia, Gianrico</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2002-09</date><risdate>2002</risdate><volume>283</volume><issue>3</issue><spage>C1001</spage><epage>C1008</epage><pages>C1001-C1008</pages><issn>0363-6143</issn><abstract>Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the alpha(1C) L-type calcium channel subunit (Ca(V)1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a beta(2) calcium channel subunit in HEK-293 or Chinese hamster ovary cells. The heterologously expressed human cardiac alpha(1C) splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the alpha(1C) COOH terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming alpha(1C)-subunit.</abstract><cop>United States</cop><pmid>12176756</pmid><doi>10.1152/ajpcell.00140.2002</doi></addata></record> |
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subjects | Animals Calcium Channels, L-Type - biosynthesis Calcium Channels, L-Type - drug effects Calcium Channels, L-Type - genetics Cell Line CHO Cells Cloning, Molecular Cricetinae Enzyme Inhibitors - pharmacology Humans Ion Channel Gating - drug effects Jejunum - metabolism Kidney - cytology Kidney - metabolism Membrane Potentials - drug effects Membrane Potentials - physiology Molecular Sequence Data Organ Specificity - physiology Patch-Clamp Techniques Pressure Protein Isoforms - biosynthesis Protein Isoforms - drug effects Protein Isoforms - genetics Protein Structure, Tertiary - physiology Protein Subunits Sequence Deletion Signal Transduction - drug effects Signal Transduction - physiology Space life sciences Stress, Mechanical Transfection |
title | alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation |
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