Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra
The effects of mefenamic acid on both membrane potential and K+ currents in pig urethral myocytes were investigated using patch‐clamp techniques (conventional whole‐cell, cell‐attached, outside‐out and inside‐out configuration). In the current‐clamp mode, mefenamic acid caused a concentration‐depend...
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| description | The effects of mefenamic acid on both membrane potential and K+ currents in pig urethral myocytes were investigated using patch‐clamp techniques (conventional whole‐cell, cell‐attached, outside‐out and inside‐out configuration).
In the current‐clamp mode, mefenamic acid caused a concentration‐dependent hyperpolarization, which was inhibited by preapplication of 1 μM glibenclamide. In the voltage‐clamp mode, mefenamic acid induced an outward current that was blocked by glibenclamide even in the presence of iberiotoxin (IbTX, 300 nM) at −50 mV.
ATP‐sensitive K+ channels (KATP channels) could be activated in the same patch by mefenamic acid and levcromakalim, with the same unitary amplitude and the similar opening gating at −50 mV in cell‐attached configuration.
In outside‐out recording, external application of mefenamic acid activated intracellular Ca2+‐activated IbTX‐sensitive large‐conductance K+ channels (BKCa channels).
Mefenamic acid (30 μM) activated spontaneous transient outward currents (STOCs). In contrast, mefenamic acid (100 μM) increased sustained outward currents, diminishing the activity of STOCs.
Over the whole voltage range, mefenamic acid caused opposite effects on the membrane currents in the absence and presence of 5 μM glibenclamide. In the presence of 10 mM 4‐aminopyridine (4‐AP), mefenamic acid only increased the outward currents.
These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4‐AP‐sensitive K+ channels in pig urethral myocytes.
British Journal of Pharmacology (2003) 140, 1341–1350. doi:10.1038/sj.bjp.0705524 |
| doi_str_mv | 10.1038/sj.bjp.0705524 |
| format | Article |
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In the current‐clamp mode, mefenamic acid caused a concentration‐dependent hyperpolarization, which was inhibited by preapplication of 1 μM glibenclamide. In the voltage‐clamp mode, mefenamic acid induced an outward current that was blocked by glibenclamide even in the presence of iberiotoxin (IbTX, 300 nM) at −50 mV.
ATP‐sensitive K+ channels (KATP channels) could be activated in the same patch by mefenamic acid and levcromakalim, with the same unitary amplitude and the similar opening gating at −50 mV in cell‐attached configuration.
In outside‐out recording, external application of mefenamic acid activated intracellular Ca2+‐activated IbTX‐sensitive large‐conductance K+ channels (BKCa channels).
Mefenamic acid (30 μM) activated spontaneous transient outward currents (STOCs). In contrast, mefenamic acid (100 μM) increased sustained outward currents, diminishing the activity of STOCs.
Over the whole voltage range, mefenamic acid caused opposite effects on the membrane currents in the absence and presence of 5 μM glibenclamide. In the presence of 10 mM 4‐aminopyridine (4‐AP), mefenamic acid only increased the outward currents.
These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4‐AP‐sensitive K+ channels in pig urethral myocytes.
British Journal of Pharmacology (2003) 140, 1341–1350. doi:10.1038/sj.bjp.0705524</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0705524</identifier><identifier>PMID: 14623761</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; ATP‐sensitive K+ channels ; Biological and medical sciences ; BKCa channels ; Female ; In Vitro Techniques ; KATP channel openers ; Large-Conductance Calcium-Activated Potassium Channels ; Medical sciences ; mefenamic acid ; Mefenamic Acid - pharmacology ; Membrane Potentials - drug effects ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - physiology ; Patch-Clamp Techniques ; Pharmacology. Drug treatments ; Potassium Channels - drug effects ; Potassium Channels - physiology ; Potassium Channels, Calcium-Activated - physiology ; Swine ; Urethra - drug effects ; Urethra - physiology ; urethral myocytes</subject><ispartof>British journal of pharmacology, 2003-12, Vol.140 (8), p.1341-1350</ispartof><rights>2003 British Pharmacological Society</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2003</rights><rights>Copyright 2003, Nature Publishing Group 2003 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4872-27639a5149bb0a5d95e34b24fd0a539e36cb5cd41b0ebf6c2515d73c956a0fd73</citedby><cites>FETCH-LOGICAL-c4872-27639a5149bb0a5d95e34b24fd0a539e36cb5cd41b0ebf6c2515d73c956a0fd73</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/PMC1574151/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574151/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15366939$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14623761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teramoto, N</creatorcontrib><creatorcontrib>Brading, A F</creatorcontrib><creatorcontrib>Ito, Y</creatorcontrib><title>Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The effects of mefenamic acid on both membrane potential and K+ currents in pig urethral myocytes were investigated using patch‐clamp techniques (conventional whole‐cell, cell‐attached, outside‐out and inside‐out configuration).
In the current‐clamp mode, mefenamic acid caused a concentration‐dependent hyperpolarization, which was inhibited by preapplication of 1 μM glibenclamide. In the voltage‐clamp mode, mefenamic acid induced an outward current that was blocked by glibenclamide even in the presence of iberiotoxin (IbTX, 300 nM) at −50 mV.
ATP‐sensitive K+ channels (KATP channels) could be activated in the same patch by mefenamic acid and levcromakalim, with the same unitary amplitude and the similar opening gating at −50 mV in cell‐attached configuration.
In outside‐out recording, external application of mefenamic acid activated intracellular Ca2+‐activated IbTX‐sensitive large‐conductance K+ channels (BKCa channels).
Mefenamic acid (30 μM) activated spontaneous transient outward currents (STOCs). In contrast, mefenamic acid (100 μM) increased sustained outward currents, diminishing the activity of STOCs.
Over the whole voltage range, mefenamic acid caused opposite effects on the membrane currents in the absence and presence of 5 μM glibenclamide. In the presence of 10 mM 4‐aminopyridine (4‐AP), mefenamic acid only increased the outward currents.
These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4‐AP‐sensitive K+ channels in pig urethral myocytes.
British Journal of Pharmacology (2003) 140, 1341–1350. doi:10.1038/sj.bjp.0705524</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>ATP‐sensitive K+ channels</subject><subject>Biological and medical sciences</subject><subject>BKCa channels</subject><subject>Female</subject><subject>In Vitro Techniques</subject><subject>KATP channel openers</subject><subject>Large-Conductance Calcium-Activated Potassium Channels</subject><subject>Medical sciences</subject><subject>mefenamic acid</subject><subject>Mefenamic Acid - pharmacology</subject><subject>Membrane Potentials - drug effects</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channels - drug effects</subject><subject>Potassium Channels - physiology</subject><subject>Potassium Channels, Calcium-Activated - physiology</subject><subject>Swine</subject><subject>Urethra - drug effects</subject><subject>Urethra - physiology</subject><subject>urethral myocytes</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkU1v1DAYhC1ERZeFK0dkIcEFZfG3kwsSrYBWFMEBzpbj2F1HTpzaCaX_vq42osClJ9t6n3c8owHgBUY7jGj9Lve7tp92SCLOCXsENphJUXFa48dggxCSFcZ1fQye5twjVIaSPwHHmAlCpcAb0H5dwuynYKF1zpo5w-jgYJ0d9eAN1MZ3MI7wy1tolpTsWAA_wjzEOO_hsGRTNo0NIUOX4gAnfwmnFH_7QQe4JDvvk34GjpwO2T5fzy34-enjj9Oz6uLb5_PTDxeVYbUkFZGCNppj1rQt0rxruKWsJcx15UUbS4VpuekYbpFtnTCEY95JahouNHLltgXvD7rT0g62M8Vs0kFNqZhJNypqr_6djH6vLuMvhblkmOMi8GYVSPFqsXlWg8934fRo45KVxIwxjkgBX_0H9nFJYwmnCJa4FrJk2YLdATIp5pys--MEI3XXncq9Kt2ptbuy8PJv__f4WlYBXq-AzkYHl_RofL7nOBWioU3h6IG79sHePPCtOvl-xjgh9BZyYbQP</recordid><startdate>200312</startdate><enddate>200312</enddate><creator>Teramoto, N</creator><creator>Brading, A F</creator><creator>Ito, Y</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200312</creationdate><title>Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra</title><author>Teramoto, N ; Brading, A F ; Ito, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4872-27639a5149bb0a5d95e34b24fd0a539e36cb5cd41b0ebf6c2515d73c956a0fd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>ATP‐sensitive K+ channels</topic><topic>Biological and medical sciences</topic><topic>BKCa channels</topic><topic>Female</topic><topic>In Vitro Techniques</topic><topic>KATP channel openers</topic><topic>Large-Conductance Calcium-Activated Potassium Channels</topic><topic>Medical sciences</topic><topic>mefenamic acid</topic><topic>Mefenamic Acid - pharmacology</topic><topic>Membrane Potentials - drug effects</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channels - drug effects</topic><topic>Potassium Channels - physiology</topic><topic>Potassium Channels, Calcium-Activated - physiology</topic><topic>Swine</topic><topic>Urethra - drug effects</topic><topic>Urethra - physiology</topic><topic>urethral myocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teramoto, N</creatorcontrib><creatorcontrib>Brading, A F</creatorcontrib><creatorcontrib>Ito, Y</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teramoto, N</au><au>Brading, A F</au><au>Ito, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2003-12</date><risdate>2003</risdate><volume>140</volume><issue>8</issue><spage>1341</spage><epage>1350</epage><pages>1341-1350</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>The effects of mefenamic acid on both membrane potential and K+ currents in pig urethral myocytes were investigated using patch‐clamp techniques (conventional whole‐cell, cell‐attached, outside‐out and inside‐out configuration).
In the current‐clamp mode, mefenamic acid caused a concentration‐dependent hyperpolarization, which was inhibited by preapplication of 1 μM glibenclamide. In the voltage‐clamp mode, mefenamic acid induced an outward current that was blocked by glibenclamide even in the presence of iberiotoxin (IbTX, 300 nM) at −50 mV.
ATP‐sensitive K+ channels (KATP channels) could be activated in the same patch by mefenamic acid and levcromakalim, with the same unitary amplitude and the similar opening gating at −50 mV in cell‐attached configuration.
In outside‐out recording, external application of mefenamic acid activated intracellular Ca2+‐activated IbTX‐sensitive large‐conductance K+ channels (BKCa channels).
Mefenamic acid (30 μM) activated spontaneous transient outward currents (STOCs). In contrast, mefenamic acid (100 μM) increased sustained outward currents, diminishing the activity of STOCs.
Over the whole voltage range, mefenamic acid caused opposite effects on the membrane currents in the absence and presence of 5 μM glibenclamide. In the presence of 10 mM 4‐aminopyridine (4‐AP), mefenamic acid only increased the outward currents.
These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4‐AP‐sensitive K+ channels in pig urethral myocytes.
British Journal of Pharmacology (2003) 140, 1341–1350. doi:10.1038/sj.bjp.0705524</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>14623761</pmid><doi>10.1038/sj.bjp.0705524</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; PMC (PubMed Central); Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); Alma/SFX Local Collection |
| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology ATP‐sensitive K+ channels Biological and medical sciences BKCa channels Female In Vitro Techniques KATP channel openers Large-Conductance Calcium-Activated Potassium Channels Medical sciences mefenamic acid Mefenamic Acid - pharmacology Membrane Potentials - drug effects Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - physiology Patch-Clamp Techniques Pharmacology. Drug treatments Potassium Channels - drug effects Potassium Channels - physiology Potassium Channels, Calcium-Activated - physiology Swine Urethra - drug effects Urethra - physiology urethral myocytes |
| title | Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethra |
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