超极化活化环核苷酸门孔通道与心脏生物起搏器(第二部分)

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 (HCN14) 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.

超极化活化环核苷酸门孔通道与心脏生物起搏器

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.

AIM:The 50-Hz magnetic field (MF) is a potential health-risk factor.Its effects on the cardiovascular system have not been fully investigated .This study was conducted to explore the effects of long-term exposure to 50-Hz MF on the cardiovascular system . METHODS:In the study , an exposure system was constructed and the distribution of 50-Hz MF was detected .Sixty-four Sprague-Dawley (SD) rats were exposed to 50-Hz MF at 100 μT for 24 weeks, 20 hours per day, while another 64 rats were sham exposed. During the exposure, blood pressure was measured every 4 weeks, and 24 weeks later, echocardiography, cardiac catheterisation and electrocardiography were performed .Moreover , heart and body weight were recorded , while haematoxylin-eosin staining and real-time PCR were conducted .RESULTS:The results showed that compared with the sham group , exposure to 50-Hz MF did not exert any effect on blood pressure, pulse rate, heart rate and cardiac rhythm.Further, echocardiography and cardiac catheterisation showed that there were no significant differences in the cardiac morphology and haemodynamics .In addition , histopathological examination showed that 50-Hz MF exposure had no effect on the structure of hearts .Finally, the expression of the cardiac hypertrophic relative genes did not show any significant differences between 50-Hz MF exposure group and the sham group .CONCLUSION: Taken together , in SD rats, exposure to 50-Hz/100-μT MF for 24 weeks did not show any obvious effects on the cardiovascular system .