Contributions of Ca(2+)-influx via the L-type Ca(2+)-current and Ca(2+)-release from the sarcoplasmic reticulum to [Ca2+]i-transients in human myocytes.
Experiments were performed to determine the relative contributions of direct Ca(2+)-entry through the L-type Ca(2+)-current and of Ca(2+)-release from the sarcoplasmic reticulum (s.r.) to the intracellular [Ca2+]i-transient in isolated human atrial and ventricular myocytes from patients with severe heart failure and from non-failing controls. Cells were isolated from explanted hearts of patients undergoing transplantation because of severe heart failure due to dilated or ischemic cardiomyopathy or from donor hearts which could not be transplanted for technical reasons. Ca(2+)-current densities were -2.1 +/- 0.6 pA/pF in atrial cells, -4.8 +/- 0.5 pA/pF in cells from patients with heart failure and -3.2 +/- 0.5 pA/pF in non-failing controls. [Ca2+]i-transients were significantly smaller in heart failure (370 +/- 33 nM) compared to ventricular cells from non-failing hearts (760 +/- 69 nM, p < 0.05). Atrial myocytes had average [Ca2+]i-transients of 505 +/- 38 nM. After incubation in ryanodine the average [Ca2+]i-transients were not significantly different between different cell types. The results indicate that the relative contribution of Ca(2+) released from the sarcoplasmic reticulum to the [Ca2+]i-transient is significantly smaller in heart failure. The absolute contribution of the L-type Ca(2+)-current to the transient seemed to be comparable in all cell types investigated. As the [Ca2+]i-transient in the presence of ryanodine was comparable in size in all cells, changes of the intracellular [Ca2+]i-transient in heart failure are mainly due to alterations of s.r. function in these cells.
Beuckelmann
D J
DJ
Department of Medicine III, University of Cologne, Germany.
D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002303:Cardiac Output, Low / Q000503:physiopathology; D004553:Electric Conductivity; D005260:Female; D006325:Heart Atria; D006352:Heart Ventricles; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D012433:Ryanodine; D002118:Calcium