Upregulation of CaMKIIδ during ischaemia-reperfusion is associated with reperfusion-induced arrhythmias and mechanical dysfunction of the rat heart: involvement of sarcolemmal Ca2+-cycling proteins
| Autor: | Tana Ravingerova, S Carnicka, Tomas Rajtik, Svec P, Adriana Adameova, Adrian Szobi, Nemčeková M |
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| Rok vydání: | 2012 |
| Předmět: |
Chronotropic
Inotrope Male medicine.medical_specialty Benzylamines Calcium Channels L-Type Physiology Ischemia Myocardial Reperfusion Injury In Vitro Techniques Sodium-Calcium Exchanger Sarcolemma Downregulation and upregulation Physiology (medical) Internal medicine Ca2+/calmodulin-dependent protein kinase medicine Animals L-type calcium channel Rats Wistar Protein Kinase Inhibitors Pharmacology Sulfonamides Sodium-calcium exchanger Chemistry Myocardium Arrhythmias Cardiac Heart General Medicine medicine.disease Rats Up-Regulation Disease Models Animal Endocrinology Ventricular fibrillation cardiovascular system Calcium-Calmodulin-Dependent Protein Kinase Type 2 |
| Zdroj: | Canadian journal of physiology and pharmacology. 90(8) |
| ISSN: | 1205-7541 |
| Popis: | Although Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) has been implicated in development of different phenotypes of myocardial ischaemia–reperfusion injury, its involvement in arrhythmogenesis and cardiac stunning is not sufficiently elucidated. Moreover, the mechanisms by which CaMKIIδ mediates disturbances in excitation–contraction coupling, are not exactly known. To investigate this, KN-93 (0.5 µmol/L), a CaMKII inhibitor, was administered before induction of global ischaemia and reperfusion in isolated Langendorff-perfused rat hearts. Expression of CaMKIIδ and the sarcollemal Ca2+-cycling proteins, known to be activated during reperfusion, was analyzed using immunoblotting. KN-93 reduced reperfusion-induced ectopic activity and the incidence of ventricular fibrillation. Likewise, the severity of arrhythmias was lower in KN-treated hearts. During the pre-ischaemia phase, neither inotropic nor chronotropic effects were elicited by KN-93, whereas post-ischaemic contractile recovery was significantly improved. Ischaemia–reperfusion increased the expression of CaMKIIδ and sodium–calcium exchanger (NCX1) proteins without any influence on the protein content of alpha 1c, a pore-forming subunit of L-type calcium channels (LTCCs). On the other hand, inhibition of CaMKII normalized changes in the expression of CaMKIIδ and NCX1. Taken together, CaMKIIδ seems to regulate its own turnover and to be an important component of cascade integrating NCX1, rather than LTCCs that promote ischaemia–reperfusion-induced contractile dysfunction and arrhythmias. |
| Databáze: | OpenAIRE |
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