Fatty acid block of the transient outward current in adult human atrium

Fatty acids represent an essential source of fuel for the heart and play an important role in the mechanical, electrical, and synthetic activities of cardiac cells. Under pathological conditions, such as ischemia followed by reperfusion, the myocardium is exposed to very high levels of fatty acids, in particular the monounsaturated fatty acid, oleic acid. Elevated plasma f atty acids have been linked to an increased risk for cardiac arrhythmias. I n other species, fatty acids have been shown to modulate several cardiac io n channels, most notably potassium channels. Virtually nothing is known abo ut the actions of oleic acid on potassium channels in human heart. We there fore characterized the effects of oleic acid on the transient outward curre nt, sustained current, and inwardly rectifying current, some of the major p otassium channels present in human atrium, using the whole-cell patch clamp method. Exposure of cells to oleic acid (5 mu M) reduced the transient out ward potassium current to 3.7 +/- 0.8 pA/pF (n = 4) compared with 7.0 +/- 0 .7 pA/pF (n = 4) (P < .05) for cells not exposed. In contrast, oleic acid h ad little effect on either the sustained current (4.3 +/- 0.3 pA/pF, n = 4 for oleic acid versus 4.8 +/- 0.5, n = 5 for control) present after the dec ay of the transient outward current or on the amplitude of I-kappa 1 measur ed at -100 mV (1.4 +/- 0.4 pA/pF, n = 4 for oleic acid versus 1.3 +/- 0.4 p A/pF, n = 6 for control). In addition, oleic acid significantly slowed the rate of recovery of the transient outward current, which is predicted to re sult in a use-dependent reduction in current amplitude in the beating heart . These results suggest a possible contributing role for oleic acid block o f the transient outward current in the pathological consequences of myocard ial ischemia.