| dc.contributor.advisor | Maier, Lars S. Prof. Dr. | |
| dc.contributor.author | Gupta, Shamindra Nath | |
| dc.date.accessioned | 2013-10-25T09:12:15Z | |
| dc.date.available | 2013-11-06T23:50:04Z | |
| dc.date.issued | 2013-10-25 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0001-BBFF-7 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4092 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Die Effekte der Ca2+-Calmodulin-abhängigen Proteinkinase II (CaMKII) auf die Aktionspotential-morphologie bei mechanischer Last | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | The effects of Calcium2+/Calmodulin-dependent protein kinase II (CaMKII) on action potential morphology under mechanical load | de |
| dc.contributor.referee | Klinge, Lars Prof. Dr. | |
| dc.date.examination | 2013-10-29 | |
| dc.description.abstracteng | The Calcium2+/Calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine protein kinase and acts as a key regulator of excitation contraction coupling in cardiac myocytes. There are several Isoforms known, with CaMKIIδ and γ being primarily expressed in heart muscle. Of these two the δ isoform is the predominant one .
Implications have been made to the role of CaMKII regarding heart failure, arrhythmias and cardiac remodeling. An inhibition of CaMKII has been suggested as a therapeutic approach but other isoforms play a vital role in other organs.
The present study specifically investigates the role of CaMKIIδ for cardiomyocyte function in a model of increased mechanical load, differentiating between increased afterload (TAC) and increased pre-load (shunt) for the role of single cell action potential morphology and arrhythmias.
In TAC mice action potential duration was significantly increased compared to sham over both tested time periods, an early one, 7 days after operation, and a late one, 21 days after operation. After CaMKII inhibition with AIP (autocamtide II- inhibitory peptide) the increased action potential duration was reduced to control levels. To further investigate the ion channel responsible for the prolongation, 2 known targets of CaMKII, the L-type calcium channel (LTCC) and the sodium channel (INa) were specifically inhibited using Nifedipine and Ranolazine, respectively. Both sets of experiments showed a significant reduction in action potential duration (APD) although the reduction with Nifedipine was remarkedly higher. Added together the reduction was almost the same level as in the AIP group.
In shunt mice in contrast no significant difference could be seen.
In summary, the APD prolongation seems to be driven by an increase in CaMKII activity in TAC mice via effects on LTCC and INA, as these were reversible with AIP. | de |
| dc.contributor.coReferee | Oppermann, Martin Prof. Dr. | |
| dc.contributor.thirdReferee | Oppermann, Martin Prof. Dr. | |
| dc.subject.eng | Calcium2+/Calmodulin-dependent protein kinase II (CaMKII) | de |
| dc.subject.eng | excitation contraction coupling | de |
| dc.subject.eng | action potential duration | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BBFF-7-4 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.subject.gokfull | Kardiologie (PPN619875755) | de |
| dc.description.embargoed | 2013-11-06 | |
| dc.identifier.ppn | 770538452 | |