LPA is secreted from numerous cell types, such as platelets, fibroblasts, and ovarian cancer cells, and is present in very small amounts in human serum. It functions both as a component of the cell membrane and as an intracellular phospholipid signaling molecule as an autocrine or paracrine mediator. Numerous and diverse biological processes are mediated by LPA, including cellular proliferation, cellular migration, differentiation, anti-apoptosis, actin cytoskeletal rearrangements, platelet aggregation, calcium mobilization, and neurotransmitter release. LPA’s biological functions are mediated by at least six G protein-coupled receptors referred to as LPA1–6, which are widely distributed in the brain, heart, kidney, spleen and other organs. These receptors couple to multiple G proteins, notably G12/13, Gi, Gq, and possibly Gs. LPA activates multiple signaling cascades, including phosphoinositide 3-kinase, phospholipase C, mitogen-activated protein kinase, Rho family GTPase, and adenylyl cyclase. Interestingly, as one of its roles as an extracellular mediator, LPA has also been proposed to serve as an endogenous activator of the nuclear peroxisome proliferator activated receptor gamma. The assignment of specific biological functions to individual GPCR subtypes has been hampered by the overlapping expression of LPA receptors, their coupling to multiple G-proteins and their regulation of diverse signal transduction pathways. These characteristics result in pleiotropic responses in functional experiments, depending the cell type and the relative expression of LPA receptors. LPA has important functions in the cardiovascular system, such as the induction of vascular smooth muscle contraction, the promotion of platelet aggregation, the stimulation of vascular smooth muscle cell and cardiac fibroblast proliferation, the promotion of cardiac hypertrophy, and the modulation of myocardial contractility. Western blot and Northern blot analysis have indicated that the whole Endothelium Differentiation Gene /LPA receptor family is expressed ubiquitously throughout the cardiovascular system. Thus, LPA may play a role in modulating cardiac function under physiological and/or pathological conditions. However, the importance of LPA in regulating ion currents in myocardiocytes has not been studied. This work, using isolated myocardial preparations, examines the effects of LPA on action potential duration and membrane currents, and analyzes the possible underlying mechanisms. Overall, this study demonstrates that LPA is a key electrophysiological Dabrafenib mediator in myocardiocytes. Lysophosphatidic acid is an intermediate metabolite of phospholipid biosynthesis and functions as an intercellular lipid messenger. Although LPA is widely reported to modulate multiple ion currents in some cell types, little was known about its electrophysiological effects on cardiac myocytes. LPA has multiple activities in the cardiovascular system. It has been shown that LPA is involved in the processes of artherosclerosis and thrombogenesis. LPA has also been found to regulate blood vessel tone, to have positive inotropic effects in the heart in rats, and to induce a hypertrophic response in cultured neonatal myocardiocytes through various signaling pathways. However, prior to this study, there had been no investigation on the potential actions of LPA on electrophysiological regulation of ion currents and APD in cardiac myocytes. In addition, LPA has been shown to activate Cl2 current in cultured corneal keratocytes in a dose-dependent manner, which results in subsequent depolarization of the cells.