Force‐frequency Relationship and Early Relaxation Kinetics Are Preserved Upon SR Blockade in Human Myocardium

Abstract

Cardiomyocytes utilize calcium to activate their myofilaments and shorten, which at the organ level results in blood being pumped out of the heart and into the body. Sarcoplasmic reticulum (SR) is an organelle in cardiomyocytes that stores calcium ions and releases them during systole, when myofilament needs to be activated and sequesters them during diastole, when myofilament needs to be deactivated. Therefore, it is believed to play an integral role in the calcium handling of cardiomyocytes with potential implications in the force‐frequency relationship, as intracellular calcium is increased at higher heart rates. However, the SR is believed to be less important in calcium handling in larger mammals, which have sodium calcium exchangers (NCX) that can extrude calcium out of cardiomyocytes. We hypothesized that when the SR is blocked in human trabeculae, the relaxation function would not be affected and that force‐frequency relationship would be preserved. We isolated intact human right ventricular trabeculae from non‐failing and failing human hearts and measured various contractile and relaxation parameters upon SR blockade. We found that force‐frequency relationship is preserved even when the SR is blocked. We also found that early relaxation speed is not affected when the SR is blocked, probably because of NCX compensating for the lack of SR function. Moreover, we found that the contraction kinetics are slower upon SR blockade, potentially because L‐type calcium channel, which have slower calcium‐release kinetics than the SR, compensates for the lack of SR calcium releaseSupport or Funding InformationR01 HL113084 to Paul ML JanssenAHA 16PRE33410549 to Jae‐Hoon ChungThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.