Key Points
- To determine whether failing ventricular myocytes exhibit an absolute increase in Na+-Ca2+ exchange density and function, rather than solely a relative increase due to impaired sarcoplasmic reticulum Ca2+ uptake.
- Isolated left ventricular midmyocardial myocytes from normal dogs and dogs with tachycardic pacing-induced heart failure.
- Measured NCX current density and Ca2+ extrusion during caffeine application under fixed (200 nmol/L) and minimal (50 µmol/L indo-1) intracellular Ca2+ buffering.
- Assessed bidirectional NCX currents and Ca2+ transport using voltage-clamp recordings while blocking sarcoplasmic reticulum Ca2+ uptake with thapsigargin.
- NCX current density showed no significant change in failing myocytes when intracellular Ca2+ was buffered to 200 nmol/L.
- Ca2+ extrusion via NCX during caffeine application doubled in failing cells compared to normal cells under minimal Ca2+ buffering.
- Both reverse-mode and forward-mode NCX currents and Ca2+ transport increased >2-fold in failing cells when sarcoplasmic reticulum uptake was blocked.
Structured PICO
PPopulationLeft ventricular midmyocardial myocytes isolated from normal or tachycardic pacing-induced failing canine hearts
IInterventionIntracellular Ca2+ buffering manipulation and sarcoplasmic reticulum (SR) uptake blockade with thapsigargin
CComparatorMyocytes from normal canine hearts
OOutcomeNa+-Ca2+ exchange (NCX) density and function (Ca2+ extrusion, reverse-mode and forward-mode NCX currents)surrogate
The study provides evidence for an absolute, intracellular calcium-dependent increase in Na+-Ca2+ exchange function in failing canine heart myocytes.