Background—Altered excitation-contraction (E-C) coupling in canine pacing-induced heart failure involves decreased sarcoplasmic reticulum (SR) Ca uptake and enhanced Na/Ca exchange, which could be expected to decrease SR Ca content (Ca_SR) and may explain the reduced intracellular Ca (Ca_i) transient. Studies in other failure models have suggested that the intrinsic coupling between L-type Ca current (I_Ca,L) and SR Ca release is reduced without a change in SR Ca load. The present study investigates whether Ca_SR and/or coupling is altered in midmyocardial myocytes from failing canine hearts (F).

Methods and Results—Myocytes were indo-1–loaded via patch pipette (37°C), and Ca_i transients were elicited with voltage-clamp steps applied at various frequencies. I_Ca,L density was not significantly decreased in F, but steady-state Ca_i transients were reduced to 20% to 40% of normal myocytes (N). Ca_SR, measured by integrating Na/Ca exchange currents during caffeine-induced release, was profoundly decreased in F, to 15% to 25% of N. When Ca_SR was normalized in F by preloading in 5 mmol/L external Ca before a test pulse at 2 mmol/L Ca, a normal-amplitude Ca_i transient was elicited. E-C coupling gain was dependent on Ca_SR but was affected similarly in both groups, indicating that intrinsic coupling is unaltered in F.

Conclusions—A decrease in Ca_SR is sufficient to explain the diminished Ca_i transients in F, without a change in the effectiveness of coupling. Therefore, therapeutic approaches that increase Ca_SR may be able to fully correct the Ca handling deficit in heart failure.