Why Are Diastolic Ca2+ Sparks Increased in Frequency in LVH Cardiomyopathy?
The observed increase in diastolic Ca2+ spark frequency in LVH is unexpected because of the measured decrease in cell-wide SR Ca2+ content. Others have clearly demonstrated that as SR Ca2+ content increases, Ca2+ spark frequency increases.17,21,22 The tendency of SR Ca2+ release increases as a power function of the SR Ca2+ content, (release ∝ loadn, where n >3).23,24 Mechanistically the increase in Ca2+ spark rate that is widely observed is thought to develop because as Ca2+ in the SR increases, the sensitivity of RyRs to be triggered by Ca2+ increases,21,25 a finding that is supported by Ca2+ spark modeling.26 However, we observe an increase in Ca2+ spark rate with a decrease in SR Ca2+ content. One hypothesis that may explain our findings is that the RyRs become more sensitive to [Ca2+]i for some other reason. In heart failure, several groups have reported that the RyR2 becomes more completely phosphorylated18 and such phosphorylation increases the sensitivity of the RyR2 in a compli
