Heart Care Info - Heart Disease Prevention & Treatment

Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats

OJ Kemi, N Mac Quaide, MA Hoydal... - Journal of Cellular ..., 2012 - Wiley Online Library Impaired cardiac control of intracellular diastolic Ca 2+ gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca 2+ handling in heart failure, the effect on diastolic Ca 2+ remains unstudied. Here, we studied the effect of exercise training on the ...

The finding that exercise training almost fully reversed the spontaneous Ca2+ release in the failing heart may provide a treatment strategy for the arrhythmogenesis observed in HF (American Heart Association, 2010). Specifically, exercise training reduced both the generation and propagation of spontaneous Ca2+ waves in the post MI HF cardiomyocytes, under both normal extracellular [Ca2+] and while the cell was challenged by high extracellular Ca2+, suggesting that the open probability of the Ry R2 is modulated. This effect has previously only been reported in diabetic cardiomyopathy (Stolen et al., 2009). However, the finding that exercise training also increased the ability of the cardiomyocytes to prevent propagation by aborting Ca2+ waves is novel. These effects could be attributable to several factors, including modulation of Ry R2 gating as a consequence of altered SR Ca2+ load or Ry R2 stability and Ca2+ sensitivity, as well as modulation of SR Ca2+ uptake by SERCA2a. The latter possibility is supported by exercise training also increasing the rate of Ca2+ wave decay and by exercise training restoring expression levels of SERCA2a in post MI HF (Wisloff et al., 2002). The fact that post MI HF also associated with reduced velocity of the propagating Ca2+ wave; whereas exercise training normalized this, may have been linked to architectural remodeling and reverse remodeling of the cardiomyocyte, which also occurs in these phenotypes (Kemi et al., 2011). In contrast, our experiments suggest that cardiomyocyte NOS derived NO does not contribute toward the observed effects. This mechanism was suggested by experiments showing that NO modulates several aspects of cardiomyocyte Ca2+ cycling including Ry R2 open probability, due to physical and chemical interactions between the Ry R2 and the endothelial and neural isoforms of NOS (Vila Petroff et al., 2001; Lim et al., 2008). Moreover, the NO effect on SR Ca2+ release is also modulated by exercise training (Hoydal et al., 2007). However, at least under the present experimental conditions, we could not detect a role of NOS derived NO on the generation and propagation of spontaneous Ca2+ waves, although inhibition of NOS did reduce the decay rate of Ca2+ waves, which suggests an effect on SERCA2a and is in line with previous studies (Hoydal et al., 2007).