Abstract
Lysophosphatidic acid (LPA) has diverse actions on the cardiovascular system and is widely reported to modulate multiple ion currents in some cell types. However, little is known about its electrophysiological effects on cardiac myocytes. This study investigated whether LPA has electrophysiological effects on isolated rabbit myocardial preparations. The results indicate that LPA prolongs action potential duration at 90% repolarization (APD90) in a concentration- and frequency-dependent manner in isolated rabbit ventricular myocytes. The application of extracellular LPA significantly increases the coefficient of APD90 variability. LPA increased L-type calcium current (ICa,L) density without altering its activation or deactivation properties. In contrast, LPA has no effect on two other ventricular repolarizing currents, the transient outward potassium current (Ito) and the delayed rectifier potassium current (IK). In arterially perfused rabbit left ventricular wedge preparations, the monophasic action potential duration, QT interval, and Tpeak-end are prolonged by LPA. LPA treatment also significantly increases the incidence of ventricular tachycardia induced by S1S2 stimulation. Notably, the effects of LPA on action potentials and ICa,L are PTX-sensitive, suggesting LPA action requires a Gi-type G protein. In conclusion, LPA prolongs APD and increases electrophysiological instability in isolated rabbit myocardial preparations by increasing ICa,L in a Gi protein-dependent manner.
Highlights
Lysophosphatidic acid (LPA) is an intermediate molecule produced during phospholipid metabolism
The data reveal that LPA prolongs action potential duration (APD) in a concentration- and frequencydependent manner (Fig. 1)
DAPD90 is the difference between APD recorded at a constant frequency before and after LPA addition (DAPD90 = APD90 pre-LPA – APD90 post-LPA)
Summary
Lysophosphatidic acid (LPA) is an intermediate molecule produced during phospholipid metabolism. A water-soluble glycerol phospholipid with a simple structure, LPA is secreted from numerous cell types, such as platelets, fibroblasts, and ovarian cancer cells [1,2], and is present in very small amounts in human serum (with a concentration of 1–5 mM). It functions both as a component of the cell membrane and as an intracellular phospholipid signaling molecule [3] as an autocrine or paracrine mediator. These characteristics result in pleiotropic responses in functional experiments, depending the cell type and the relative expression of LPA receptors [13]
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