Objective To study the effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein(PY) sleeve cardiomyocytes with atrial fibrillation.Methods Dissociation of PVs yielded single cardiomy...Objective To study the effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein(PY) sleeve cardiomyocytes with atrial fibrillation.Methods Dissociation of PVs yielded single cardiomyocytes from a Landengorff column without or with pacemaker activity from long-term rapidly atrial pacing (RAP) canines.If current was measured with the whole-cell patch-clamp technique.Results Compared with the control group,the rapidly atrial pacing canine PV cardiomyocytes had spontaneous diastolic depolarization and had larger If densities.Ivabradine (Iva,1 μM),a selective inhibitor of the If current,markedly reduced If currents in the RAP from -2.66±0.4 pA/pF to -1.58±0.1 pA/pF at the test potential of-120 mV (P＜0.01,n=12).Inhibition effect of Iva of If current showed concentration-dependent range from 0.1 to 10.0μM,with IC50 of 2.2 μ M ( 1.8-2.9 μM,95% CL).Furthermore,V1/ of steady-state activated curve was shifted from -84.3±4.9 mV to -106.9±3.4 mV and k value of steady-state activated curve was changed from 12.1+2.6 mV to 9.9±3.4 mV by the application of.1.0 μM Iva ( P＜0.01,n=12).Conclusions Our study revealed that Ivarbadine may significantly decrease If of rapidly atrial pacing pulmonary vein sleeve ceUs with atrial fibdllation.(J Geriatr Cardiol 2008;5:39-42)展开更多
Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current ( named Ⅰf, Ⅰh, or Ⅰq). Recent studies have unveiled ...Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current ( named Ⅰf, Ⅰh, or Ⅰq). Recent studies have unveiled the molecular identity of HCN (HCN1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ⅰh and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in,the development of biological pacemakers.展开更多
Abstract Hyperpolarization-activated cyclic-nucleotide-gated ( HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current (named If, Ih, or Iq). Recent studies have unv...Abstract Hyperpolarization-activated cyclic-nucleotide-gated ( HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current (named If, Ih, or Iq). Recent studies have unveiled the molecular identity of HCN (HCN 1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ih and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in the development of biological pacemakers.展开更多
基金the National NaturalScience Foundation of China(No: 30570739)
文摘Objective To study the effect of ivabradine on hyperpolarization activated cation current in canine pulmonary vein(PY) sleeve cardiomyocytes with atrial fibrillation.Methods Dissociation of PVs yielded single cardiomyocytes from a Landengorff column without or with pacemaker activity from long-term rapidly atrial pacing (RAP) canines.If current was measured with the whole-cell patch-clamp technique.Results Compared with the control group,the rapidly atrial pacing canine PV cardiomyocytes had spontaneous diastolic depolarization and had larger If densities.Ivabradine (Iva,1 μM),a selective inhibitor of the If current,markedly reduced If currents in the RAP from -2.66±0.4 pA/pF to -1.58±0.1 pA/pF at the test potential of-120 mV (P＜0.01,n=12).Inhibition effect of Iva of If current showed concentration-dependent range from 0.1 to 10.0μM,with IC50 of 2.2 μ M ( 1.8-2.9 μM,95% CL).Furthermore,V1/ of steady-state activated curve was shifted from -84.3±4.9 mV to -106.9±3.4 mV and k value of steady-state activated curve was changed from 12.1+2.6 mV to 9.9±3.4 mV by the application of.1.0 μM Iva ( P＜0.01,n=12).Conclusions Our study revealed that Ivarbadine may significantly decrease If of rapidly atrial pacing pulmonary vein sleeve ceUs with atrial fibdllation.(J Geriatr Cardiol 2008;5:39-42)
基金the National Natural Science Foundation of China(No.30470559,30330230,30240059)the National Basic Research Development Program(973)of China(No.2007CB512501)Beijing Natural Science Foundation(No.7052039)
文摘Dorsal root ganglion(DRG)neurons have peripheral terminals in skin,muscle,and other peripheral tissues,andcentral
文摘Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current ( named Ⅰf, Ⅰh, or Ⅰq). Recent studies have unveiled the molecular identity of HCN (HCN1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ⅰh and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in,the development of biological pacemakers.
文摘Abstract Hyperpolarization-activated cyclic-nucleotide-gated ( HCN) channels in the heart modulate cardiac automaticity via the hyperpolarization-activated cation current (named If, Ih, or Iq). Recent studies have unveiled the molecular identity of HCN (HCN 1-4) channels. HCN isoforms are unevenly expressed in the heart, even in the sinoatrial node. Features of HCN currents have been characterized in cardiac and other types of cells or in cell lines transfected with the HCN isoforms. The factors modulating Ih and the physiological significance of HCN channels in the heart have been extensively investigated in recent years. The hypothesis for transplanting and/or creating biological pacemakers to replace diseased sinoatrial and/or atrioventricular nodes has been postulated and tested in animal models. Local overexpression of HCN2 channels in the left atrium or in the left conductive bundle branch of the left ventricle via gene delivery induced significant Ih and escape rhythms during vagal stimulation in canines. In addition, implantation of human mesenchymal stem cells with overexpression of HCN2 channels to the canine left ventricular wall was associated with formation of spontaneous escape rhythms of left-sided origin during vagal-stimulation-induced sinus arrest. This preliminary data suggest that the use of HCN channels may hold great promise in the development of biological pacemakers.
