Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs.
Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties....
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Song, Tao [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021transfer abstract |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a - Liao, Gary ELSEVIER, 2020, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:139 ; year:2021 ; pages:0 |
| Links: |
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| DOI / URN: |
10.1016/j.biopha.2021.111581 |
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| 245 | 1 | 0 | |a Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. |
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| 520 | |a Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. | ||
| 520 | |a Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. | ||
| 650 | 7 | |a Negative chronotropic action |2 Elsevier | |
| 650 | 7 | |a Resibufogenin |2 Elsevier | |
| 650 | 7 | |a Ion channels |2 Elsevier | |
| 650 | 7 | |a Conduction velocity |2 Elsevier | |
| 650 | 7 | |a Species-difference |2 Elsevier | |
| 700 | 1 | |a Li, Jiajia |4 oth | |
| 700 | 1 | |a Wang, Mingye |4 oth | |
| 700 | 1 | |a Su, Min |4 oth | |
| 700 | 1 | |a Xu, Dengfeng |4 oth | |
| 700 | 1 | |a Zhou, Luheng |4 oth | |
| 700 | 1 | |a Zhang, Xiaopei |4 oth | |
| 700 | 1 | |a Wang, Hongtao |4 oth | |
| 700 | 1 | |a Hou, Yunlong |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier Science |a Liao, Gary ELSEVIER |t A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a |d 2020 |g Amsterdam [u.a.] |w (DE-627)ELV004620771 |
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10.1016/j.biopha.2021.111581 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001569.pica (DE-627)ELV054218128 (ELSEVIER)S0753-3322(21)00366-8 DE-627 ger DE-627 rakwb eng 610 VZ 44.86 bkl Song, Tao verfasserin aut Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. 2021transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Negative chronotropic action Elsevier Resibufogenin Elsevier Ion channels Elsevier Conduction velocity Elsevier Species-difference Elsevier Li, Jiajia oth Wang, Mingye oth Su, Min oth Xu, Dengfeng oth Zhou, Luheng oth Zhang, Xiaopei oth Wang, Hongtao oth Hou, Yunlong oth Enthalten in Elsevier Science Liao, Gary ELSEVIER A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a 2020 Amsterdam [u.a.] (DE-627)ELV004620771 volume:139 year:2021 pages:0 https://doi.org/10.1016/j.biopha.2021.111581 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.86 Hämatologie VZ AR 139 2021 0 |
| spelling |
10.1016/j.biopha.2021.111581 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001569.pica (DE-627)ELV054218128 (ELSEVIER)S0753-3322(21)00366-8 DE-627 ger DE-627 rakwb eng 610 VZ 44.86 bkl Song, Tao verfasserin aut Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. 2021transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Negative chronotropic action Elsevier Resibufogenin Elsevier Ion channels Elsevier Conduction velocity Elsevier Species-difference Elsevier Li, Jiajia oth Wang, Mingye oth Su, Min oth Xu, Dengfeng oth Zhou, Luheng oth Zhang, Xiaopei oth Wang, Hongtao oth Hou, Yunlong oth Enthalten in Elsevier Science Liao, Gary ELSEVIER A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a 2020 Amsterdam [u.a.] (DE-627)ELV004620771 volume:139 year:2021 pages:0 https://doi.org/10.1016/j.biopha.2021.111581 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.86 Hämatologie VZ AR 139 2021 0 |
| allfields_unstemmed |
10.1016/j.biopha.2021.111581 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001569.pica (DE-627)ELV054218128 (ELSEVIER)S0753-3322(21)00366-8 DE-627 ger DE-627 rakwb eng 610 VZ 44.86 bkl Song, Tao verfasserin aut Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. 2021transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Negative chronotropic action Elsevier Resibufogenin Elsevier Ion channels Elsevier Conduction velocity Elsevier Species-difference Elsevier Li, Jiajia oth Wang, Mingye oth Su, Min oth Xu, Dengfeng oth Zhou, Luheng oth Zhang, Xiaopei oth Wang, Hongtao oth Hou, Yunlong oth Enthalten in Elsevier Science Liao, Gary ELSEVIER A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a 2020 Amsterdam [u.a.] (DE-627)ELV004620771 volume:139 year:2021 pages:0 https://doi.org/10.1016/j.biopha.2021.111581 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.86 Hämatologie VZ AR 139 2021 0 |
| allfieldsGer |
10.1016/j.biopha.2021.111581 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001569.pica (DE-627)ELV054218128 (ELSEVIER)S0753-3322(21)00366-8 DE-627 ger DE-627 rakwb eng 610 VZ 44.86 bkl Song, Tao verfasserin aut Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. 2021transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Negative chronotropic action Elsevier Resibufogenin Elsevier Ion channels Elsevier Conduction velocity Elsevier Species-difference Elsevier Li, Jiajia oth Wang, Mingye oth Su, Min oth Xu, Dengfeng oth Zhou, Luheng oth Zhang, Xiaopei oth Wang, Hongtao oth Hou, Yunlong oth Enthalten in Elsevier Science Liao, Gary ELSEVIER A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a 2020 Amsterdam [u.a.] (DE-627)ELV004620771 volume:139 year:2021 pages:0 https://doi.org/10.1016/j.biopha.2021.111581 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.86 Hämatologie VZ AR 139 2021 0 |
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10.1016/j.biopha.2021.111581 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001569.pica (DE-627)ELV054218128 (ELSEVIER)S0753-3322(21)00366-8 DE-627 ger DE-627 rakwb eng 610 VZ 44.86 bkl Song, Tao verfasserin aut Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. 2021transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. Negative chronotropic action Elsevier Resibufogenin Elsevier Ion channels Elsevier Conduction velocity Elsevier Species-difference Elsevier Li, Jiajia oth Wang, Mingye oth Su, Min oth Xu, Dengfeng oth Zhou, Luheng oth Zhang, Xiaopei oth Wang, Hongtao oth Hou, Yunlong oth Enthalten in Elsevier Science Liao, Gary ELSEVIER A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a 2020 Amsterdam [u.a.] (DE-627)ELV004620771 volume:139 year:2021 pages:0 https://doi.org/10.1016/j.biopha.2021.111581 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.86 Hämatologie VZ AR 139 2021 0 |
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Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs. |
| abstract |
Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. |
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Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. |
| abstract_unstemmed |
Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD 20 , APD 50 , and APD 90 at 100 μM and inhibited calcium currents (I Ca ), total outward potassium currents (I K ), and transient outward potassium current (I to ) in a concentration-dependent manner, but not on the inward rectifying potassium current (I K1 ). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on I Kr in hERG-HEK293 cells was detected. The IC 50 of RGB on I Kr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the I to on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su. |
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