Ryanodine perfusion decreases cardiac mechanical function without affecting homogenate sarcoplasmic reticulum Ca2+ uptake: comparison with the stunned heart.
This study tested the hypothesis that perfusion with low concentrations of ryanodine, which opens the sarcoplasmic reticulum (SR) Ca2+ channel in a sub-conducting state, could mimic the effects of stunning on both mechanical and SR activity. Perfusion of isolated rat hearts with 10-160 nM ryanodine progressively decreased left ventricular developed pressure (LVDP) and increased end-diastolic pressure (EDP), but LVDP decreased more and EDP increased less than in the stunned heart. The effect of ryanodine perfusion on LVDP and EDP is consistent with the opening of the SR Ca2+ channel by high-affinity ryanodine binding, reducing SR Ca2+ content and interfering with mechanical function. In contrast to stunning, ryanodine perfusion did not affect the homogenate Ca2+ uptake rates measured in the presence or absence of high [ryanodine]. Perfusion with 80 nM 3H-ryanodine resulted in a large decline in LVDP, but only a small degree of ryanodine binding. Thus, prolonged opening of only a few channels affects the SR in situ, whereas this is undetectable in the homogenate. Higher levels of ryanodine binding (0.3 pmol/mg) to the in vitro homogenate also did not affect the homogenate Ca(2+)-uptake rate in the presence or absence of high [ryanodine], whereas it reduced the stimulation of Ca2+ uptake by ruthenium red. High-affinity ryanodine binding to the SR Ca2+ channel, either by perfusion or by binding after homogenisation, did not duplicate the increased Ca2+ efflux observed in the stunned heart, suggesting that the SR defect in the stunned heart is not a prolonged opening of a sub-conducting state of the SR Ca2+ channel.
Wu
Q Y
QY
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Feher
J J
JJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000473:pathology / Q000503:physiopathology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000008:administration & dosage*; D012519:Sarcoplasmic Reticulum / Q000473:pathology / Q000502:physiology*
D012433:Ryanodine; D002118:Calcium