Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in ...Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.展开更多
Aim Evidence has shown that stimulation of alA-adrenorecetors receptor （alA-AR） or angiotensin II type 1 receptor （AT1R） acutely down-regulates the rapid component of the delayed rectifier K ＋ current （IKr） via...Aim Evidence has shown that stimulation of alA-adrenorecetors receptor （alA-AR） or angiotensin II type 1 receptor （AT1R） acutely down-regulates the rapid component of the delayed rectifier K ＋ current （IKr） via protein kinase C （PKC）. This study was designed to investigate which PKC isozymes mediate down-regulations of IKr by alA-AR and AT1R. Method The whole-cell patch-clamp technique was used to record IKr in native cardio- myocytes and in human embryonic kidney （HEK） 293 cells co-transfected with human ether-a-go-go related gene （hERG） encoding α-subunit of IKr and human alA-AR or AT1R gene. Result In isolated guinea-pig ventricular cardiomyocytes the inhibitory action of Ang II on IKr was little affected by Go6976 （selectively inhibiting PKCα, β and γ） and Go6983 （selectively inhibiting PKCα, β, γ , δ, and ζ）, but was significantly antagonized by an inter- nal dialysis with PKCe-selective inhibitory peptide εV1 -2. In contrast, the inhibitory action of alA-AR agonist A61603 on IKr was remarkably attenuated by Go6976 or Go6983, but not affected by peptide εV1 -2. Moreover, specific PKC-selective inhibitory peptide antagonized the effect of A61603. The results suggested that PKCe and PKCα isoform respectively mediated the inhibitory effect of AT1R and a1A-AR. In heterologous expression system, both PKCα and e-selective activator peptides down regulated hERG current with different manner. PKCα activator peptide shifted the activation curve of the channel to the right, but PKCe-selective activator peptide did not. Simi- larly, A61603 shifted the activation curve to the right, whereas Ang Ⅱ had no effect. In addition, both A61603 and PKCα activator peptide showed inhibitory action on bERG A PKC current （an bERG mutant in which 17 of the 18 ROSITE-predicted PKC acceptor serines/threonines were changed to alanine） with a similar potency to wild type bERG current. But, both Ang Ⅱ and PKCe-selective activator peptide exhibited no effects on bERG △ PKC cur- rent. The results indicated that PKCα and PKCe isoforms down-regulated bERG current through different mecha- nism. Conclusion PKCα and PKCe isoform respectively mediates the inhibition on IKr by stimulation of AT1R and alA-AR via different molecular mechanism.展开更多
Objective： To study the effect of Xinjining extract （心悸宁, XJN） on inward rectifier potassium current （IKI） in ventricular myocyte （VMC） of guinea pigs and its anti-arrhythmic mechanism on ion channel level. ...Objective： To study the effect of Xinjining extract （心悸宁, XJN） on inward rectifier potassium current （IKI） in ventricular myocyte （VMC） of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Methods： Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the Ikl in VMC irrigated with XJN of different concentrations （1.25, 2.50, 5.00 g/L; six samples for each）. The stable current and conductance of the inward component of IK1 as well as the outward component of peak IK1 and conductance of it accordingly was recorded when the test voltage was set on -110 mV. Results： The suppressive rate of XJN on the inward component of IK1 was 9.54% ± 5.81%, 34.82% ± 15.03%, and 59.52% ± 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak IK1 was 23.94%± 7.45%, 52.98%± 19.62%, and 71.42% ± 23.01%, respectively （all P〈0.05）. Moreover, different concentrations of XJN also showed effects for reducing IK1 conductance. Conclusion： XJN has inhibitory effect on IK1in guinea pig＇s VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.30700747)
文摘Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.
文摘Aim Evidence has shown that stimulation of alA-adrenorecetors receptor （alA-AR） or angiotensin II type 1 receptor （AT1R） acutely down-regulates the rapid component of the delayed rectifier K ＋ current （IKr） via protein kinase C （PKC）. This study was designed to investigate which PKC isozymes mediate down-regulations of IKr by alA-AR and AT1R. Method The whole-cell patch-clamp technique was used to record IKr in native cardio- myocytes and in human embryonic kidney （HEK） 293 cells co-transfected with human ether-a-go-go related gene （hERG） encoding α-subunit of IKr and human alA-AR or AT1R gene. Result In isolated guinea-pig ventricular cardiomyocytes the inhibitory action of Ang II on IKr was little affected by Go6976 （selectively inhibiting PKCα, β and γ） and Go6983 （selectively inhibiting PKCα, β, γ , δ, and ζ）, but was significantly antagonized by an inter- nal dialysis with PKCe-selective inhibitory peptide εV1 -2. In contrast, the inhibitory action of alA-AR agonist A61603 on IKr was remarkably attenuated by Go6976 or Go6983, but not affected by peptide εV1 -2. Moreover, specific PKC-selective inhibitory peptide antagonized the effect of A61603. The results suggested that PKCe and PKCα isoform respectively mediated the inhibitory effect of AT1R and a1A-AR. In heterologous expression system, both PKCα and e-selective activator peptides down regulated hERG current with different manner. PKCα activator peptide shifted the activation curve of the channel to the right, but PKCe-selective activator peptide did not. Simi- larly, A61603 shifted the activation curve to the right, whereas Ang Ⅱ had no effect. In addition, both A61603 and PKCα activator peptide showed inhibitory action on bERG A PKC current （an bERG mutant in which 17 of the 18 ROSITE-predicted PKC acceptor serines/threonines were changed to alanine） with a similar potency to wild type bERG current. But, both Ang Ⅱ and PKCe-selective activator peptide exhibited no effects on bERG △ PKC cur- rent. The results indicated that PKCα and PKCe isoforms down-regulated bERG current through different mecha- nism. Conclusion PKCα and PKCe isoform respectively mediates the inhibition on IKr by stimulation of AT1R and alA-AR via different molecular mechanism.
基金Supported by the Fundfor Innovation of Phenomof Henan Province(No.0521002400)
文摘Objective： To study the effect of Xinjining extract （心悸宁, XJN） on inward rectifier potassium current （IKI） in ventricular myocyte （VMC） of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Methods： Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the Ikl in VMC irrigated with XJN of different concentrations （1.25, 2.50, 5.00 g/L; six samples for each）. The stable current and conductance of the inward component of IK1 as well as the outward component of peak IK1 and conductance of it accordingly was recorded when the test voltage was set on -110 mV. Results： The suppressive rate of XJN on the inward component of IK1 was 9.54% ± 5.81%, 34.82% ± 15.03%, and 59.52% ± 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak IK1 was 23.94%± 7.45%, 52.98%± 19.62%, and 71.42% ± 23.01%, respectively （all P〈0.05）. Moreover, different concentrations of XJN also showed effects for reducing IK1 conductance. Conclusion： XJN has inhibitory effect on IK1in guinea pig＇s VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.
