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(Circulation. 2001;104:2645.)
© 2001 American Heart Association, Inc.

Brief Rapid Communications

Phospholipid Metabolite 1-Palmitoyl-Lysophosphatidylcholine Enhances Human Ether-a-Go-Go-Related Gene (HERG) K⁺ Channel Function

Jingxiong Wang, MD; Huizhen Wang, MD; Hong Han, MD, PhD; Yiqiang Zhang, MSc; Baofeng Yang, MD, PhD; Stanley Nattel, MD; Zhiguo Wang, PhD

From the Research Center, Montreal Heart Institute, Montreal, Canada (J.W., H.W., H.H., Y.Z., Z.W.); the Department of Medicine, University of Montreal, Montreal, Canada (J.W., Y.Z., Z.W.); the Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada (S.N.); and the Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang, China (B.Y.).

Correspondence to Zhiguo Wang, Research Center, Montreal Heart Institute, 5000 Belanger East, Montreal, PQ H1T 1C8 Canada. E-mail wzmail{at}canada.com

Background— Lysophosphatidylcholine (LPC), a naturally occurring phospholipid metabolite, accumulates in the ischemic heart and causes extracellular K⁺ accumulation and action potential shortening. LPC has been incriminated as a biochemical trigger of lethal cardiac arrhythmias, but the underlying mechanisms remain poorly understood.

Methods and Results— We studied the effect of 1-palmitoyl-LPC (Pal-LPC) on currents resulting from human ether-a-go-go-related gene (HERG) expression in human embryonic kidney (HEK) cells using whole-cell patch-clamp techniques. Bath application of Pal-LPC consistently and reversibly increased HERG current (I_HERG). The effects of Pal-LPC were apparent as early as 3 minutes after application of the drug, reached maximum within 10 minutes, and were reversible on washout. Pal-LPC increased I_HERG at voltages between -20 and +30 mV, with greater effects at stronger depolarization. However, Pal-LPC did not affect the voltage-dependence of I_HERG activation. In contrast, Pal-LPC significantly shifted the inactivation curve toward more positive potentials, causing a mean 20.0±2.2 mV shift in half-inactivation voltage relative to control.

Conclusions— Our results indicate that apart from being a well-recognized target for drug inhibition, I_HERG can also be enhanced by natural substances. An increase in I_HERG by Pal-LPC may contribute to K⁺ loss, abnormal electrophysiology, and arrhythmia occurrence in the ischemic heart.

Key Words: lysophosphatidylcholines • ion channels • patch-clamp techniques

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