Altered sarcolemmal calcium channel density and Ca(2+)-pump ATPase activity in tachycardia heart failure.
Whether sarcolemmal (SL) calcium handling is altered in endstage heart failure produced by chronic rapid pacing is not known. To investigate this we paced 7 rabbits at a rate of 400 beats/min for 35 +/- 11 days. 6 animals served as non-paced controls. Purified left ventricular SL membranes were then prepared and tested for [3H]-nitrendipine binding and (Ca(2+) + Mg2+)-dependent ATPase (Ca(2+)-pump) activity. Results show a 50% reduction in calcium channel antagonist binding sites with Bmax values reduced from 450 +/- 40 to 230 +/- 8 fmoles/mg protein in response to chronic rapid pacing (P < 0.01). This change was accompanied by a modest decrease in Kd from 0.29 +/- 0.09 to 0.22 +/- 0.03 nM (not significant). Vmax values for the SL Ca(2+)-pump ATPase were decreased from 387 to 164 nmoles/mg protein/min (P < 0.01) with KCa2+ values reduced from 0.91 to 0.28 microM Ca2+ (P < 0.05) in response to tachycardia induced failure as compared to controls. ATPase activity in both groups was very sensitive to 25 microM calmidazolium and 5 microM vanadate. Results from this study indicate that both a reduction in SL calcium channel density and decrease in SL Ca(2+)-pump ATPase activity are evident in tachycardia heart failure. We conclude that sarcolemmal calcium handling is altered in heart failure induced by chronic rapid pacing and that such changes may contribute to systolic dysfunction associated with this model to heart failure.
Department of Medicine, University of Texas Health Science Center at San Antonio.
J T
JT
Colston
P
P
Kumar
J P
JP
Chambers
G L
GL
Freeman
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007537:Isometric Contraction; D007700:Kinetics; D009568:Nitrendipine / Q000378:metabolism; D011817:Rabbits; D012508:Sarcolemma / Q000201:enzymology / Q000378:metabolism*; D013599:Systole; D013610:Tachycardia / Q000150:complications; D014638:Vanadates / Q000494:pharmacology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007093:Imidazoles; D014638:Vanadates; C031938:calmidazolium; D009568:Nitrendipine; D000252:Calcium-Transporting ATPases; D002118:Calcium