The air pollutant phenanthrene disrupts calcium cycling and alters repolarization in female sheep ventricular cardiomyocytes.

Multiple epidemiological studies link cardiac dysfunction with increased levels of air pollution. While cellular mechanisms underlying such dysfunction are yet to be fully elucidated, a proposed mediator of this effect is phenanthrene, a 3-ringed polycyclic aromatic hydrocarbon (PAH). Here, we used ventricular myocytes freshly isolated from healthy female sheep (Ovis aries) to study the impact of acute phenanthrene exposure on cardiac electrophysiology and intracellular Ca(2+) cycling in a large mammalian model. We observed ~37% (n = 11) shortening of the action potential duration (APD) at 90% repolarization following exposure to 25 μM phenanthrene. This APD shortening occurred despite a concentration-dependent inhibition of the delayed rectifier potassium current (I(Kr)), with maximal inhibition of ~56% with 25 μM phenanthrene. Phenanthrene also reduced the calcium transient amplitude by ~40% (n = 10), slowed the rate of calcium transient decay by ~60% (n = 10), but had no effect on the peak current amplitude of I(Ca). Notably, preincubation of ventricular myocytes with pharmacological agents that inhibit sarcoplasmic reticulum calcium cycling by inhibiting SERCA activity and ryanodine receptor function prevented phenanthrene-dependent changes in the calcium transient amplitude and time-course. Together, these data show acute exposure to phenanthrene impairs electrical activity and intracellular calcium cycling in ventricular myocytes of healthy sheep.