Ryanodine receptor dysfunction and triggered activity in the heart
| Autor: | Gregory S. Hoeker, Toshiyuki Oya, Kenneth R. Laurita, Rodolphe Katra |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Heart disease Physiology Sudden death Membrane Potentials Dogs Heart Conduction System Physiology (medical) Internal medicine medicine Animals Calcium Signaling Calcium signaling Membrane potential business.industry Extramural Ryanodine receptor Arrhythmias Cardiac Heart Ryanodine Receptor Calcium Release Channel musculoskeletal system medicine.disease Endocrinology Circulatory system cardiovascular system Calcium Cardiology and Cardiovascular Medicine business tissues |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 292:H2144-H2151 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00924.2006 |
| Popis: | Arrhythmogenesis has been increasingly linked to cardiac ryanodine receptor (RyR) dysfunction. However, the mechanistic relationship between abnormal RyR function and arrhythmogenesis in the heart is not clear. We hypothesize that, under abnormal RyR conditions, triggered activity will be caused by spontaneous calcium release (SCR) events that depend on transmural heterogeneities of calcium handling. We performed high-resolution optical mapping of intracellular calcium and transmembrane potential in the canine left ventricular wedge preparation ( n = 28). Rapid pacing was used to initiate triggered activity under normal and abnormal RyR conditions induced by FKBP12.6 dissociation and β-adrenergic stimulation (20–150 μM rapamycin, 0.2 μM isoproterenol). Under abnormal RyR conditions, almost all preparations experienced SCRs and triggered activity, in contrast to control, rapamycin, or isoproterenol conditions alone. Furthermore, under abnormal RyR conditions, complex arrhythmias (monomorphic and polymorphic tachycardia) were commonly observed. After washout of rapamycin and isoproterenol, no triggered activity was observed. Surprisingly, triggered activity and SCRs occurred preferentially near the epicardium but not the endocardium ( P < 0.01). Interestingly, the occurrence of triggered activity and SCR events could not be explained by cytoplasmic calcium levels, but rather by fast calcium reuptake kinetics. These data suggest that, under abnormal RyR conditions, triggered activity is caused by multiple SCR events that depend on the faster calcium reuptake kinetics near the epicardium. Furthermore, multiple regions of SCR may be a mechanism for multifocal arrhythmias associated with RyR dysfunction. |
| Databáze: | OpenAIRE |
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