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 (Ca2++Mg2+)-dependent ATPase (Ca2+-pump) activity. Results show a 50% reduction in calcium channel antagonist binding sites with Bmaxvalues 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 Kdfrom 0.29 ± 0.09 to 0.22 ± 0.03 nM (not significant). Vmaxvalues for the SL Ca2+-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 μM Ca2+(P < 0.05) in response to tachycardia induced failure as compared to controls. ATPase activity in both groups was very sensitive to 25 μM calmidazolium and 5 μM vanadate. Results from this study indicate that both a reduction in SL calcium channel density and decrease in SL Ca2+-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 of heart failure. © 1994.
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