Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current
Objective To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). Methods and results Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic...
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| Veröffentlicht in: | Pacing and clinical electrophysiology 2024-09, Vol.47 (9), p.1131-1140 |
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| container_title | Pacing and clinical electrophysiology |
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| creator | Zhang, Feng Fan, Jianing Lei, Fuhua Liu, Tao Lin, Dawei Qin, Mu Cheng, Wenbo |
| description | Objective
To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs).
Methods and results
Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol‐12‐myristate‐13‐acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p |
| doi_str_mv | 10.1111/pace.14998 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3072797958</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3072797958</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2468-4471fd6581bf75d8eca3821b4a64760bfc1cf74aeeb157125fbacaa82db04963</originalsourceid><addsrcrecordid>eNp9kctO3DAUhi0EKsNlwwMgS2wQKNROnNhejiJ6ESOVBXvLcY4Zo0wSbGfQ7PoIfcY-CR6GdsGCs7F09PnTr_MjdEbJDU3zddQGbiiTUuyhGS0ZyQQt5T6aEcp4JgohD9FRCE-EkIqw8gs6TKs8lwWfIT830a11dEOPB4vv72qsrQUTA45LwGvoo3dm6rTHHkJ0cXpDRz-M4KODgHXfYu39chOXq-EReghu-9cP0-MSL_7-_hM3I-BaX2MzeZ98J-jA6i7A6ft7jB6-3T7UP7LFr-8_6_kiMzmrRMYYp7atSkEby8tWgNGFyGnDdMV4RRprqLGcaYCGlpzmpW200VrkbUOYrIpjdLnTpqzPU8quVi4Y6DrdwzAFVRCec8llKRJ68QF9Gibfp3CqoLmUtOByS13tKOOHEDxYNXq30n6jKFHbItS2CPVWRILP35VTs4L2P_rv8gmgO-DFdbD5RKXu5_XtTvoKTqeV0g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3129913798</pqid></control><display><type>article</type><title>Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Zhang, Feng ; Fan, Jianing ; Lei, Fuhua ; Liu, Tao ; Lin, Dawei ; Qin, Mu ; Cheng, Wenbo</creator><creatorcontrib>Zhang, Feng ; Fan, Jianing ; Lei, Fuhua ; Liu, Tao ; Lin, Dawei ; Qin, Mu ; Cheng, Wenbo</creatorcontrib><description>Objective
To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs).
Methods and results
Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol‐12‐myristate‐13‐acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch‐clamp, peak amplitude of L‐type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans.
Conclusion
PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.</description><identifier>ISSN: 0147-8389</identifier><identifier>ISSN: 1540-8159</identifier><identifier>EISSN: 1540-8159</identifier><identifier>DOI: 10.1111/pace.14998</identifier><identifier>PMID: 38922937</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acetic acid ; Action potential ; Action Potentials - drug effects ; Animals ; Ca2+ current ; Calcium Channels, L-Type - metabolism ; Calcium currents ; Calcium influx ; Cytotoxicity ; Kinases ; Lymphocytes T ; Male ; Protein kinase C ; Protein Kinase C - metabolism ; Rabbits ; Restitution ; spatial heterogeneity ; Tachycardia, Ventricular - physiopathology ; Ventricle ; ventricular tachyarrhythmia ; Verapamil</subject><ispartof>Pacing and clinical electrophysiology, 2024-09, Vol.47 (9), p.1131-1140</ispartof><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2468-4471fd6581bf75d8eca3821b4a64760bfc1cf74aeeb157125fbacaa82db04963</cites><orcidid>0000-0002-1952-2701</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpace.14998$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpace.14998$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38922937$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Fan, Jianing</creatorcontrib><creatorcontrib>Lei, Fuhua</creatorcontrib><creatorcontrib>Liu, Tao</creatorcontrib><creatorcontrib>Lin, Dawei</creatorcontrib><creatorcontrib>Qin, Mu</creatorcontrib><creatorcontrib>Cheng, Wenbo</creatorcontrib><title>Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current</title><title>Pacing and clinical electrophysiology</title><addtitle>Pacing Clin Electrophysiol</addtitle><description>Objective
To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs).
Methods and results
Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol‐12‐myristate‐13‐acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch‐clamp, peak amplitude of L‐type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans.
Conclusion
PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.</description><subject>Acetic acid</subject><subject>Action potential</subject><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Ca2+ current</subject><subject>Calcium Channels, L-Type - metabolism</subject><subject>Calcium currents</subject><subject>Calcium influx</subject><subject>Cytotoxicity</subject><subject>Kinases</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Protein kinase C</subject><subject>Protein Kinase C - metabolism</subject><subject>Rabbits</subject><subject>Restitution</subject><subject>spatial heterogeneity</subject><subject>Tachycardia, Ventricular - physiopathology</subject><subject>Ventricle</subject><subject>ventricular tachyarrhythmia</subject><subject>Verapamil</subject><issn>0147-8389</issn><issn>1540-8159</issn><issn>1540-8159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctO3DAUhi0EKsNlwwMgS2wQKNROnNhejiJ6ESOVBXvLcY4Zo0wSbGfQ7PoIfcY-CR6GdsGCs7F09PnTr_MjdEbJDU3zddQGbiiTUuyhGS0ZyQQt5T6aEcp4JgohD9FRCE-EkIqw8gs6TKs8lwWfIT830a11dEOPB4vv72qsrQUTA45LwGvoo3dm6rTHHkJ0cXpDRz-M4KODgHXfYu39chOXq-EReghu-9cP0-MSL_7-_hM3I-BaX2MzeZ98J-jA6i7A6ft7jB6-3T7UP7LFr-8_6_kiMzmrRMYYp7atSkEby8tWgNGFyGnDdMV4RRprqLGcaYCGlpzmpW200VrkbUOYrIpjdLnTpqzPU8quVi4Y6DrdwzAFVRCec8llKRJ68QF9Gibfp3CqoLmUtOByS13tKOOHEDxYNXq30n6jKFHbItS2CPVWRILP35VTs4L2P_rv8gmgO-DFdbD5RKXu5_XtTvoKTqeV0g</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Zhang, Feng</creator><creator>Fan, Jianing</creator><creator>Lei, Fuhua</creator><creator>Liu, Tao</creator><creator>Lin, Dawei</creator><creator>Qin, Mu</creator><creator>Cheng, Wenbo</creator><general>Wiley Subscription Services, Inc</general><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>7TK</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1952-2701</orcidid></search><sort><creationdate>202409</creationdate><title>Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current</title><author>Zhang, Feng ; Fan, Jianing ; Lei, Fuhua ; Liu, Tao ; Lin, Dawei ; Qin, Mu ; Cheng, Wenbo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2468-4471fd6581bf75d8eca3821b4a64760bfc1cf74aeeb157125fbacaa82db04963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acetic acid</topic><topic>Action potential</topic><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Ca2+ current</topic><topic>Calcium Channels, L-Type - metabolism</topic><topic>Calcium currents</topic><topic>Calcium influx</topic><topic>Cytotoxicity</topic><topic>Kinases</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Protein kinase C</topic><topic>Protein Kinase C - metabolism</topic><topic>Rabbits</topic><topic>Restitution</topic><topic>spatial heterogeneity</topic><topic>Tachycardia, Ventricular - physiopathology</topic><topic>Ventricle</topic><topic>ventricular tachyarrhythmia</topic><topic>Verapamil</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Fan, Jianing</creatorcontrib><creatorcontrib>Lei, Fuhua</creatorcontrib><creatorcontrib>Liu, Tao</creatorcontrib><creatorcontrib>Lin, Dawei</creatorcontrib><creatorcontrib>Qin, Mu</creatorcontrib><creatorcontrib>Cheng, Wenbo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Pacing and clinical electrophysiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Feng</au><au>Fan, Jianing</au><au>Lei, Fuhua</au><au>Liu, Tao</au><au>Lin, Dawei</au><au>Qin, Mu</au><au>Cheng, Wenbo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current</atitle><jtitle>Pacing and clinical electrophysiology</jtitle><addtitle>Pacing Clin Electrophysiol</addtitle><date>2024-09</date><risdate>2024</risdate><volume>47</volume><issue>9</issue><spage>1131</spage><epage>1140</epage><pages>1131-1140</pages><issn>0147-8389</issn><issn>1540-8159</issn><eissn>1540-8159</eissn><abstract>Objective
To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs).
Methods and results
Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli–extra‐stimulus (S1–S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol‐12‐myristate‐13‐acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch‐clamp, peak amplitude of L‐type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans.
Conclusion
PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38922937</pmid><doi>10.1111/pace.14998</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1952-2701</orcidid></addata></record> |
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| subjects | Acetic acid Action potential Action Potentials - drug effects Animals Ca2+ current Calcium Channels, L-Type - metabolism Calcium currents Calcium influx Cytotoxicity Kinases Lymphocytes T Male Protein kinase C Protein Kinase C - metabolism Rabbits Restitution spatial heterogeneity Tachycardia, Ventricular - physiopathology Ventricle ventricular tachyarrhythmia Verapamil |
| title | Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L‐type Ca+ current |
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