Increased intracellular [dATP] enhances cardiac contraction in embryonic chick cardiomyocytes

AbstractAlthough ATP is the physiological substrate for cardiac contraction, cardiac contractility is significantly enhanced in vitro when only 10% of ATP substrate is replaced with 2′‐deoxy‐ATP (dATP). To determine the functional effects of increased intracellular [dATP] ([dATP]i) within living cardiac cells, we used hypertonic loading with varying exogenous dATP/ATP ratios, but constant total nucleotide concentration, to elevate [dATP]i in contractile monolayers of embryonic chick cardiomyocytes. The increase in [dATP]i was estimated from dilution of dye added in parallel with dATP. Cell viability, average contractile amplitude, rates of contraction/relaxation, spontaneous beat frequency, and Ca2+ transient amplitude and kinetics were examined. At total [dATP]i above ∼70 µM, spontaneous contractions ceased, and above ∼100 µM [dATP]i, membrane blebbing was also observed, consistent with apoptosis. Interestingly, [dATP]i of ∼60 µM (∼40% increase over basal [dATP]i levels) enhanced both amplitude of contraction and the rates of contraction and relaxation without affecting beat frequency. With total [dATP]i of ∼60 µM or less, we found no significant change in Ca2+ transients. These d