Palmitic acid enhances calcium sequestration by isolated sarcoplasmic reticulum

Abstract

Long chain fatty acids have been found to accumulate in the cytosol of the ischemic myocardium. To determine if these fatty acids might contribute to the early depression of contractile function observed in the ischemic heart, we investigated the effect of palmitic acid (PA), a C 16 saturated fatty acid, on calcium sequestration by sarcoplasmic reticulum vesicles (SR) in vitro. Calcium sequestration by rabbit skeletal and canine cardiac SR in the absence of calcium precipitating anions (“calcium binding”) was determined by Millipore filtration or by ultracentrifugation. When present from the onset of the reaction, 8 to 32 μ m PA increased the amount of calcium sequestered by 6 μg/ml SR in a concentration-dependent manner. Under control conditions 131 ± 10 nmol of Ca/mg skeletal SR protein was sequestered. In the presence of 8, 16, and 32 μ m PA, concentrations below the critical micellar concentrations of PA, calcium sequestration by skeletal SR was increased to 145 ± 4, 178 ± 22 and 362 ± 32 nmol Ca/mg SR protein respectively. A similar concentration-dependent enhancement of calcium sequestration by PA was observed in canine cardiac SR. When PA was added to skeletal SR 2 min after the start of the reaction, a time when calcium sequestration became maximal, similar concentration-dependent enhancement of calcium sequestration was observed. The ability of PA to enhance calcium sequestration by the SR could promote calcium retention within this intracellular membrane system under conditions where cytosolic PA is increased.