The Study Of The Lysophosphatidic Acid Effects On Cx43 And Ion Channels Of The Rats With Myocardial Infarction

Lysophosphatidic acid (LPA) is an intermediate product of membranous phospholipid contents. It can also be released from the activated platelets. During the acute myocardial infarction, the increase of phospholipid enzymatic activity facilitates the produce of lysophospholipids acid, which means that LPA may be related with arrhythmia occurrence. Connexin 43(Cx43) is the predominant protein in gap junction and the main gap junction protein of the ventricular myocytes. The low-resistance electrical couplings comprising with Cx43 make the ventricular myocytes contracting synchronously, which can be modulated through ion exchanges. If Cx43 reduced by 50%, the ventricular conduction velocity decrease obviously, resulting in arrhythmia.In this paper, through ligating the left lower branch of the rat left coronary artery, we find the heart rate of acute myocardial infarction of a rat model increases significantly. Seventy percent of experimental animal shows premature ventricualr contraction, which means that arrhythmia can take place in the rats with myocardial infarction. We observe through experiments that LPA can enhance the contraction of rats with myocardial infarction. Using the patch clamp recording technique, it is proved the positive inotropic mechanism from the ion channel level, which take functions through activating calcium channel L and increasing calcium channel currents, resulting in the occurrence of arrhythmia.The cardiac function is based on the law of myocardial cell signaling, which has been proved to be mediated by gap junction(GJ). Using the western blot for measuring the expression of Cx43 in the rats with acute myocardial infarction, we find that the Cx43 expression of ventricular myocytes of the rat with myocardial infarction and LPA decreased more than that of the normal rats (p<0.05). The Cx43 expression of LPA specificity blocker Ki16425 and AMI groups are enhanced obviously compared with the myocardial infarction group, which is almost same as the normal group. It is not significant for the group LPA and the normal group(p>0.05), while it is significant compared with the myocardial infarction group(p<0.05). Takingβ-actin as the parameter, every group show no significant difference(p>0.05). LPA specificity blocker can reduce the expression of Cx43. The expression of the group AMI+ Ki16425 is improved compared with the myocardial infarction group, which prove LPA can reduce the expression of Cx43. It is an important way of LPA inducing arrhythmia.The above results suggest that:(1) LPA involved in the occurrence of arrhythmia after acute myocardial infarction.(2)LPA can induce the open of the intracellular calcium ion channel, which result in the intracellular calcium overload and the generation of EADs and DADs. All of these factors can induce arrhythmia.(3)LPA can reduce the expression of Cx43 in rats with myocardial infarction, which can increase the occurrence of arrhythmia.