Nutrient restriction preserves calcium cycling and mitochondrial function in cardiac myocytes during ischemia and...

Nutrient restriction (NR) prolongs longevity via enhanced mitochondrial function. We tested the hypothesis that NR enhances resistance to ischemia/reperfusion (IR) arrhythmias via preserved calcium (Ca) cycling and mitochondrial function. We examined the protective effects of NR on regional IR in cultured neonatal rat ventricular myocyte monolayers. Optical mapping of intracellular Ca and mitochondrial membrane potential Δψ(m) was performed using Rhod 2-AM and TMRE, respectively. Regional ischemia was mimicked by covering a portion of monolayer with a glass coverslip until loss of Ca propagation, and reperfusion was mimicked by removing the coverslip. NR was mimicked by culture in serum- and glucose-free medium for 24 h. Relative to controls, NR monolayers: (1) sustained Ca oscillations during longer periods of ischemia (19.2 ± 1.8 min vs 10.4 ± 1.4 min, p<0.001); (2) had attenuated increases in Ca transient duration (CaD) and time decay constant (Tau) during ischemia; (3) had preserved conduction velocity (CV) during early reperfusion, leading to protection against reperfusion arrhythmias; (4) had minimal "rebound" decreased CaD and Tau during reperfusion; and (5) had no depolarization of Δψ(m) during IR. NR attenuates IR arrhythmias via (1) stable calcium cycling and (2) prevention of Δψ(m) depolarization during IR. Enhanced mitochondrial resistance to IR arrhythmias may play a role in NR-induced longevity prolongation.