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Alteration Of Ion Channel Currents In Ventricular Myocytes From Acute Infarcted Heart

Posted on:2003-04-25Degree:MasterType:Thesis
Country:ChinaCandidate:C DingFull Text:PDF
GTID:2144360065950234Subject:Internal Medicine
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AIM :After coronary artery occlusion ,surviving myocardium in and around the infarct zone plays an important role in arrhythmogenesis .To probe into the cellular basis of the arrhythmias ,both the current and function of Na+ channel current(lNa) L-type Ca2+ current(Ica-L) transient outward K+current(Ito) and inward rectifying K+ current(lKi) of myocardial cells from the epicardial border zone of infarcted heart were studied at the time points of 1 -week and 2-month after coronary ligation.Methods:Fifty rabbits(1.5 to 2 kg) were used in these studies. Thity-eight rabbits were infarcted by ligation of the left anterior descending coronary artery,!week as well as 2 month later, single ventricular myocytes were enzymatically dissociated and isolated ,then INa ICa L Ito and IKI were recorded using the whole cell patch-clamp techniques.Two rabbits,which the coronary artery was isolated but not ligated during the surgical procedure,served as sham control(Sham). In addition,ten rabbits that had not undergone any previous surgery as control. We compared the currents in cells from epicardial border zone of the 1-week (PMI-1W) and 2-month infarcted rabbit hearts (PMI-2M) with cells from same anatonic region of control noninfarcted hearts (CON). The infarcted region of the heart was identified on gross examination as a pale white mottlted area on the epicardial surface.Results:in : Peak INa current density(at -30mV) was significantly reduced in PMMW(22.48±4.62 PA/PF, n=14 cells) and PMI-2M (16.4+4.43 PA/PF,n=13 cells) compared with CON(45.5±5.33 PA/PF,n=12 cells), PO.Ol.This was not accompanied by a shift in the current-voltage relation . In addition,the averaged peak INa current density of sham control(44.2±4.1 PA/PF, n=7 cells)was not different from CON, P>0.05.Half-inactivation potential(V0.5) of the availability curve(I/Imax curve)was shifted significantly in the hyperpolarizing direction in PMI-1 W(-89.1 ± 5.6 mV,n=6 cells) compared with CON(-76.2±5.3 mV,n=5 cells), P<0.05. vq.s was also shifted in the same direction in PMI-2M(-84.3 ±5.7 mV,n=7 cells) compared with CON ,although this shift was not significant, P>0.05. Recovery of INa from inactivation was significantly slower in PMI-1 W compared with CON as well as PMI-2M.Both the peak INa current density and the time course of iNal-V curve were no different in Sham from CON,indicating that opration did not affect the current density.Ic-L:Peak Ica-L current density(at OmV) was significantly reduced in PMI-1 W (3.52 ±0.93 PA/ PF,n=6cells) compared with CON (5.58+1.53 PA/PF, n= 10 cells), P<0.01. However,by 2 month after occlusion,the Peak Ica-L density in PMI-2M (4.84+1.48PA/PF,n=ll cells) was no different from CON, although there was slight reduction in PMI-2M. Vo.5 of the availability curve was shifted significantly in the hyperpolarizing direction in PMI-1W (-25.9±7.0 mV, n=6 cells) compared with CON (-13.1 + 4.2 mV,n=8 cells), P<0.05.V0.5 was also shifted in the hyperpolarizing direction in PMI-2M(-21.3 + 5.6 mV, n=8 cells) compared to CON ,although this shift was not significant, p>0.05.(3) Ito :Ito current density (at +60mV) was significantly reduced in PMI-1W ( (7.47+2.39 PA/PF,n=12 cells) and PMI-2M (11.82 ±4.11 PA/PF,n=ll cells) compared with CON(17.39 + 5.24 PA/PF,n=16 cells ) ,P<0.01; Nevertheless , there was an increase in Ito current density in PMI-2M compared with PMI-1W, PO.05. iki ".iki current(at -120 mV)was also significantly reduced in PMI-1 W (3.01+0.49 nA,n=ll cells) compared with CON (4.12±0.51 nA,n=10 cells) ,P<0.05. However ,by 2 month after occlusion ,the IKi current(-120 mV) in PMI-2M(3.91+0.41 nA,n=10 cells) was no different from CON,although there was slight reduction in PMI-2M.Conclusion:CD Our studys indicate that left coronary occlusion induces significant reduction in ins > Ica-t> Ito and Ikj.Thesechanges may underlie the altered electrical activity and abnormal transmembrane action potentials of the surviving ventricular fibers of the infarcted heart,thus contributing to ventricul...
Keywords/Search Tags:Myocardial infarction, Ventricular myocytes, Patch clamp, Ion channels, Na~+ current, L-type Ca2+ current, transient outward K~+ current, inward rectifier K~+ current
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