Post-rest contraction amplitude in myocytes from failing human ventricle.
It has been reported that the balance between the two main Ca2+ removal systems in the cardiac cells, the sarcoplasmic reticulum (SR) and Na+/Ca2+ exchanger, is altered in failing human heart. We have studied post-rest contraction behaviour as a non-invasive probe of the amount of Ca2+ stored in the SR in myocytes from failing and non-failing human ventricle. The first beat following a rest interval, as a percentage of the preceding steady state (B1/SS), was larger and more variable in cells from failing heart, indicating some accumulation of Ca2+ in the SR during rest. This could be mimicked by treatment of myocytes with digoxigenin, a compound which increases intracellular Na+, suggesting that alterations in the Na+ balance of the cell might contribute to the effect. Isoprenaline, which stimulates Ca2+ uptake by the SR while the myocyte is beating, prevented SR Ca2+ accumulation during rest in susceptible myocytes. We hypothesize that loss of SR function in the failing heart is partially compensated for by increased Ca2+ extrusion via the Na+/Ca2+ exchange in the contracting myocyte, leading to increased intracellular Na+ during activity. This Na+ is lost at rest, predisposing the cells to accumulate Ca2+ in the SR. Experiments to test this hypothesis are proposed.
Davia
K
K
Imperial College of Science Technology and Medicine, London, UK.
Harding
S E
SE
D000704:Analysis of Variance; D002118:Calcium / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use; D005576:Colforsin / Q000627:therapeutic use; D004076:Digoxigenin / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000627:therapeutic use; D016014:Linear Models; D009200:Myocardial Contraction / Q000187:drug effects*; D012146:Rest / Q000502:physiology*; D019284:Thapsigargin / Q000627:therapeutic use
D002316:Cardiotonic Agents; D005576:Colforsin; D019284:Thapsigargin; D007545:Isoproterenol; D004076:Digoxigenin; D002118:Calcium