Key Points
- To elucidate the mechanisms underlying reduced sarcoplasmic reticulum (SR) Ca2+ content and depressed intracellular Ca2+ transients in intact cardiac myocytes following myocardial infarction.
- Isolated ventricular myocytes from rat hearts 3 weeks after moderate myocardial infarction (MI) or sham operation.
- Assessed in situ SR Ca2+ uptake via caffeine-induced and twitch-related half-times (t1/2) of intracellular Ca2+ transient decline, and quantified SR Ca2+-ATPase protein expression using immunoblotting.
- Measured SR Ca2+ leak in intact myocytes using an electrophysiological technique tracking the time constant of SR Ca2+ loss following thapsigargin treatment.
- Systolic intracellular Ca2+ concentration at 5.0 mM extracellular Ca2+ was significantly lower in MI myocytes compared to sham myocytes (337 ± 11 vs 416 ± 18 nM; P ≤ 0.05).
- The half-time of intracellular Ca2+ decline was prolonged by 19% in MI myocytes (0.306 ± 0.014 vs 0.258 ± 0.014 s; P ≤ 0.05), which corresponded with a 23% reduction in SR Ca2+-ATPase protein expression.
- The rate of SR Ca2+ leak did not differ between groups, showing similar time constants of Ca2+ loss after thapsigargin (268 s in MI vs 290 s in sham).
Structured PICO
PPopulationMyocytes isolated from rat hearts 3 weeks after moderate myocardial infarction (MI)
IInterventionIn situ measurement of sarcoplasmic reticulum (SR) Ca2+ uptake and SR Ca2+ leak
CComparatorMyocytes from sham-operated rats
OOutcomeSR Ca2+ uptake (measured by t(1/2) of [Ca2+]i decline) and SR Ca2+ leaksurrogate
Reduced sarcoplasmic reticulum Ca2+ content in post-MI rat myocytes is driven by decreased SR Ca2+ uptake and SR Ca2+-ATPase expression, rather than enhanced SR Ca2+ leak.