Intravenous Anesthetic Propofol Inhibits Multiple Human Cardiac Potassium Channels

AbstractAbstract Propofol blocks several important potassium currents including I Kur in human atrial myocytes or stably expressing cell lines and prolongs the action potential in human atria. The findings have particular relevance to the understanding of the potential antitachycardia and antiatrial fibrillation effects of propofol on our patients. Supplemental Digital Content is available in the text. Background: Propofol is widely used clinically for the induction and maintenance of anesthesia. Clinical case reports have shown that propofol has an antiatrial tachycardia/fibrillation effect; however, the related ionic mechanisms are not fully understood. The current study investigates the effects of propofol on human cardiac potassium channels. Methods: The whole cell patch voltage clamp technique was used to record transient outward potassium current ( I to ) and ultrarapidly activating delayed rectifier potassium current ( I Kur ) in human atrial myocytes and hKv1.5, human ether-à-go-go-related gene (hERG), and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells. Current clamp mode was used to record action potentials in human atrial myocytes. Results: In human atrial myocytes, propofol inhibited I to in a concentration-dependent manner (IC 50 = 33.5 ± 2.0 μM for peak current, n = 6) by blocking open channels without affecting the voltage-dependent kinetics or the recovery time constant; propofol decreased I Kur (IC 50 = 35.3 ± 1.9 μM, n = 6) in human atrial myocytes and inhibited hKv1.5 current expressed in HEK 293 cells by preferentially binding to the open channels. Action potential duration at 90% repolarization was slightly prolonged by 30 μM propofol in human atrial myocytes. In addition, propofol also suppressed hERG and hKCNQ1/hKCNE1 channels expressed in HEK 293 cells. Conclusion: Propofol inhibits multiple human cardiac potassium channels, including human atrial I to and I Kur , as well as hKv1.5, hERG, and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, and slightly prolongs human atrial action potential duration, which may contribute to the antiatrial tachycardia/fibrillation effects observed in patients who receive propofol.