Lysophosphatidylcholine and Cellular Potassium Loss in Isolated Rabbit Ventricle

Abstract

Background: Lysophospholipids such as lysophosphatidylcholine (LPC) have many direct electrophysiological effects on cardiac muscle and have been implicated as a cause of lethal ventricular arrhythmias during acute myocardial ischemia. Because extracellular K ⁺ accu mulation is also a key arrhythmogenic factor during acute ischemia, we examined the effects of LPC on cellular K⁺ balance, including its interaction with adenosine triphosphate- sensitive K+ (K_ATP) channels.

Methods and Results : Isolated rabbit interventricular septa paced at 75 beats/min were loaded with ⁴²K⁺ to measure unidirectional K⁺ efflux rate (in ⁴²K^- washout experiments) or tissue K ⁺ content (in ⁴²K⁺ uptake experiments) and action potential duration (APD) during exposure to 20 μM LPC for 30 minutes. LPC caused tissue K⁺ content to decrease by 15 ± 2% (n = 4) at a steady rate over 30 minutes, associated with gradual APD shortening and a delayed increase in unidirectional K⁺ efflux rate. Pretreatment with 12 μM cromakalim to selectively activate K_ATP channels shortened APD by 44 ± 66% and had no effect on net tis sue K⁺ content during control aerobic perfusion. However, cromakalim increased net K⁺ loss during exposure to LPC to 22 ± 4%, a 47% increase.

Conclusions: LPC induced net K loss in heart, which was potentiated by the K_ATP channel agonist cromakalim. This ATP finding suggests that if LPC accumulates to similar levels during myocardial ischemia and hypoxia, it may be an important mechanism in net K⁺ loss.