| Lysophosphatidic acid is a intermediary metabolite of phospholipid in cell membrane, it also releases from activated platelets. Recent studies have shown that LPA exhibits a wide spectrum of biological effects on variety cells via G-protein-coupled cell surface receptors. More studies focused on the role of LPA in physiological and pathological processes. A few studies about the effects of LPA on myocytes have been reported. there is no report about effect of LPA on ion channel in myocytes, especially the relationship between LPA and arrhythmia occurrence during myocardial ischemia. The concentration of LPA may increase in the region of ischemia during acute myocardiac infarction, because the platelets and the phospholipase are activated. PLA receptors EDG2 and EDG7 are distributed in myocytes. We propose that LPA may play an important role in arrhythmia occurrence in acute myocardiac infarction. In our study we observed the effect of LPA on ion channel in myocytes, the relationship between LPA and arrhythmia occurrence during the ischemia-reperfusion, the effect of LPA on myocytes apoptosis during the ischemia-reperfursion injury. The plasma LPA concentration of ovary cancer patients is more one hundred times higher than the concentration of normal person.We made a clinic epidemiology investigation about incidence of arrhythmia in ovary cancer. We observed that the incidence of arrhythmia of ovary cancer and hepatoma were 32.38% and 10.19% respectively. This result suggests that LPA may involve in arrhythmia occurance. We observed the effects of LPA on incidence of arrhythmia during ischemia-reperfusion injury by using a ischemia-reperfusion rat model in vivo.LPA (4mg/kg weight iv )causes the incidence of arrhythmias (ventricular premature beat and paroxysmal ventricular tachycandia) obviously increase. Compared to control group(9.21±1.92%), the frequency of ventricular arrhythmia happens in 100 heart beat(10.29±2.1%) grows much higher(P<0.05).We observed the effect of LPA on the ion channel currents in collagenase isolated ventricular myocytes of guinea pig by using patch clamp technique.Effects of LPA on the calcium channel current in guinea pig ventricular myocytes.In this part of experiment, we recorded the calcium current of 41 ventricular myocytes isolated from 14 guinea pigs. Compared to control group (n=8).LPA 0.1μmol/l group, 1μmol/l group and 10μmol/l group could increase the amplitude of calcium current significantly (p<0.01),and the percent of calcium current increasing compared control group were 28.6%(n=9), 46.2%(n=9) and 56.4%(n=8)respectively. The effects of LPA on the calcium current show dose-effect dependence relationship. After incubated in the extra cellular solution contain PTX 0.1μg/ml (n=7) in 37oC for 30 minutes, the amplitude of calcium current induced by LPA( 1μmol/l) didn't show any changes compared to the control group. The results showed LPA could increase the calcium current of ventricular myocytes, and the effect could be blocked by PTX (a kind of specific blocker of G-protein coupled receptor). We observed that LPA increase the intracellular free calcium concentration of ventricular myocytes by using fura-2 fluorescence dye. This result is consonance with the above calcium current experiment result. Effects of LPA on potassium current in guinea pig ventricular myocytes.We recorded the potassium current of 33 ventricular myocytes isolated from 13 guinea pigs. Compared to control group(n=8), LPA 1μmol/l group and 10μmol/l group could decrease the amplitude of potassium current significantly, and the percent of the potassium current decreasing compared control group were 14.4% (p<0.05) and 34.4% (P<0.01)respectively. LPA 0.1uml/L group did not show significant difference to the control group. The effects of LPA on the potassium current also showed dose-effect dependence relationship. Effect of LPA on sodium current in Guinea pig ventricular myocytes.We observed sodium current of 24 ventricular my...
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