The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells
We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels. Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells. The Kv current amplitude was inhibited by LY294002 in a dose-d...
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| Veröffentlicht in: | Life sciences (1973) 2013-05, Vol.92 (17-19), p.916-922 |
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| container_title | Life sciences (1973) |
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| creator | Hong, Da Hye Choi, Il-Whan Son, Youn Kyoung Kim, Dae-Joong Na, Sung Hun Jung, Won-Kyo Yoon, Young Wook Park, Won Sun |
| description | We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels.
Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells.
The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48μM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83±0.01μM−1s−1 and 2.59±0.14s−1, respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10μM), did not affect the Kv current, and did not change the inhibitory effect of LY294002.
Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition. |
| doi_str_mv | 10.1016/j.lfs.2013.03.006 |
| format | Article |
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Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells.
The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48μM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83±0.01μM−1s−1 and 2.59±0.14s−1, respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10μM), did not affect the Kv current, and did not change the inhibitory effect of LY294002.
Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2013.03.006</identifier><identifier>PMID: 23557854</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Androstadienes - pharmacology ; Animals ; Chromones - administration & dosage ; Chromones - pharmacology ; Coronary artery ; Coronary Vessels - cytology ; Coronary Vessels - drug effects ; Coronary Vessels - metabolism ; dissociation ; dose response ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - administration & dosage ; Enzyme Inhibitors - pharmacology ; LY294002 ; Male ; Morpholines - administration & dosage ; Morpholines - pharmacology ; myocytes ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; phosphatidylinositol 3-kinase ; Phosphatidylinositol 3-Kinase - antagonists & inhibitors ; potassium ; potassium channels ; Potassium Channels, Voltage-Gated - drug effects ; Potassium Channels, Voltage-Gated - metabolism ; Rabbits ; smooth muscle ; Voltage-dependent K+ channel</subject><ispartof>Life sciences (1973), 2013-05, Vol.92 (17-19), p.916-922</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-b156a7ebd707d24e7cb2f174aa939b1f70cf4b15bfdbd33b0540359a07cbf5553</citedby><cites>FETCH-LOGICAL-c443t-b156a7ebd707d24e7cb2f174aa939b1f70cf4b15bfdbd33b0540359a07cbf5553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2013.03.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23557854$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hong, Da Hye</creatorcontrib><creatorcontrib>Choi, Il-Whan</creatorcontrib><creatorcontrib>Son, Youn Kyoung</creatorcontrib><creatorcontrib>Kim, Dae-Joong</creatorcontrib><creatorcontrib>Na, Sung Hun</creatorcontrib><creatorcontrib>Jung, Won-Kyo</creatorcontrib><creatorcontrib>Yoon, Young Wook</creatorcontrib><creatorcontrib>Park, Won Sun</creatorcontrib><title>The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels.
Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells.
The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48μM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83±0.01μM−1s−1 and 2.59±0.14s−1, respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10μM), did not affect the Kv current, and did not change the inhibitory effect of LY294002.
Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.</description><subject>Androstadienes - pharmacology</subject><subject>Animals</subject><subject>Chromones - administration & dosage</subject><subject>Chromones - pharmacology</subject><subject>Coronary artery</subject><subject>Coronary Vessels - cytology</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - metabolism</subject><subject>dissociation</subject><subject>dose response</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>LY294002</subject><subject>Male</subject><subject>Morpholines - administration & dosage</subject><subject>Morpholines - pharmacology</subject><subject>myocytes</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>phosphatidylinositol 3-kinase</subject><subject>Phosphatidylinositol 3-Kinase - antagonists & inhibitors</subject><subject>potassium</subject><subject>potassium channels</subject><subject>Potassium Channels, Voltage-Gated - drug effects</subject><subject>Potassium Channels, Voltage-Gated - metabolism</subject><subject>Rabbits</subject><subject>smooth muscle</subject><subject>Voltage-dependent K+ channel</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LUzEUhoMoTq3-ADeapSC3nnw1vbiSwY_BgoIzC1chyT2Zpt6b1OR2QPDHm9LRpXAgWTzvy8kTQp4zWDFg6zf71RjqigMTK2gD6wdkwTa672At2EOyAOCyExzUBXlS6x4AlNLiMbngol02Si7I7-sdUgwB_UxzoF-vBP0Rk61IY9pFF-dc6PY772XrojnRuzzO9ha7AQ-YBkwz_fya-p1NCcfaMrRY11LU55KTLb-oLTOWaEdap5znHZ2O1Y9IPY5jfUoeBTtWfHZ_LsnNh_fXl5-67ZePV5fvtp2XUsydY2ptNbpBgx64RO0dD0xLa3vROxY0-CAb5MLgBiEcKAlC9RYaGJRSYklenXsPJf88Yp3NFOtpA5swH6thQmquNlJAQ9kZ9SXXWjCYQ4lTe4hhYE7Szd406eYk3UCbpnpJXtzXH92Ew7_EX8sNeHkGgs3G3pZYzc231qCgFW404414eyaaRbyLWEz1EZPHIZb2NWbI8T8L_AFdb5s6</recordid><startdate>20130520</startdate><enddate>20130520</enddate><creator>Hong, Da Hye</creator><creator>Choi, Il-Whan</creator><creator>Son, Youn Kyoung</creator><creator>Kim, Dae-Joong</creator><creator>Na, Sung Hun</creator><creator>Jung, Won-Kyo</creator><creator>Yoon, Young Wook</creator><creator>Park, Won Sun</creator><general>Elsevier Inc</general><scope>FBQ</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>7X8</scope></search><sort><creationdate>20130520</creationdate><title>The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells</title><author>Hong, Da Hye ; Choi, Il-Whan ; Son, Youn Kyoung ; Kim, Dae-Joong ; Na, Sung Hun ; Jung, Won-Kyo ; Yoon, Young Wook ; Park, Won Sun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-b156a7ebd707d24e7cb2f174aa939b1f70cf4b15bfdbd33b0540359a07cbf5553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Androstadienes - pharmacology</topic><topic>Animals</topic><topic>Chromones - administration & dosage</topic><topic>Chromones - pharmacology</topic><topic>Coronary artery</topic><topic>Coronary Vessels - cytology</topic><topic>Coronary Vessels - drug effects</topic><topic>Coronary Vessels - metabolism</topic><topic>dissociation</topic><topic>dose response</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>LY294002</topic><topic>Male</topic><topic>Morpholines - administration & dosage</topic><topic>Morpholines - pharmacology</topic><topic>myocytes</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>phosphatidylinositol 3-kinase</topic><topic>Phosphatidylinositol 3-Kinase - antagonists & inhibitors</topic><topic>potassium</topic><topic>potassium channels</topic><topic>Potassium Channels, Voltage-Gated - drug effects</topic><topic>Potassium Channels, Voltage-Gated - metabolism</topic><topic>Rabbits</topic><topic>smooth muscle</topic><topic>Voltage-dependent K+ channel</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, Da Hye</creatorcontrib><creatorcontrib>Choi, Il-Whan</creatorcontrib><creatorcontrib>Son, Youn Kyoung</creatorcontrib><creatorcontrib>Kim, Dae-Joong</creatorcontrib><creatorcontrib>Na, Sung Hun</creatorcontrib><creatorcontrib>Jung, Won-Kyo</creatorcontrib><creatorcontrib>Yoon, Young Wook</creatorcontrib><creatorcontrib>Park, Won Sun</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, Da Hye</au><au>Choi, Il-Whan</au><au>Son, Youn Kyoung</au><au>Kim, Dae-Joong</au><au>Na, Sung Hun</au><au>Jung, Won-Kyo</au><au>Yoon, Young Wook</au><au>Park, Won Sun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2013-05-20</date><risdate>2013</risdate><volume>92</volume><issue>17-19</issue><spage>916</spage><epage>922</epage><pages>916-922</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>We examined the effect of LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, on voltage-dependent K+ (Kv) channels.
Electrophysiological recordings were performed in freshly isolated rabbit coronary arterial smooth muscle cells.
The Kv current amplitude was inhibited by LY294002 in a dose-dependent manner, with a Kd value of 1.48μM. Without alteration of the kinetics of activation, LY294002 accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for LY294002 were 1.83±0.01μM−1s−1 and 2.59±0.14s−1, respectively. Application of LY294002 had no significant impact on the steady-state activation or inactivation curves. In the presence of LY294002, the recovery time constant from inactivation was increased, and Kv channel inhibition increased under train pulses (1 or 2Hz). This indicates that LY294002-induced Kv channel inhibition is use-dependent. Furthermore, pretreatment with another PI3K inhibitor, wortmannin (10μM), did not affect the Kv current, and did not change the inhibitory effect of LY294002.
Based on these results, we suggest that LY294002 directly blocks Kv current irrespective of PI3K inhibition.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>23557854</pmid><doi>10.1016/j.lfs.2013.03.006</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0024-3205 |
| ispartof | Life sciences (1973), 2013-05, Vol.92 (17-19), p.916-922 |
| issn | 0024-3205 1879-0631 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1347258430 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Androstadienes - pharmacology Animals Chromones - administration & dosage Chromones - pharmacology Coronary artery Coronary Vessels - cytology Coronary Vessels - drug effects Coronary Vessels - metabolism dissociation dose response Dose-Response Relationship, Drug Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - pharmacology LY294002 Male Morpholines - administration & dosage Morpholines - pharmacology myocytes Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinase - antagonists & inhibitors potassium potassium channels Potassium Channels, Voltage-Gated - drug effects Potassium Channels, Voltage-Gated - metabolism Rabbits smooth muscle Voltage-dependent K+ channel |
| title | The effect of PI3 kinase inhibitor LY294002 on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells |
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