Biological Pacemaker For Treatment Of Sick Sinus Syndrome

Part I The cell connection and electrophysiological basis of the sinoatrial nodeBackground Recent years, while the construction of biological pacemaker by molecular biology techniques has became hot, understanding the mechanisms of the sionatrial node pacemaker activity seems important. A variety of ion channels are involved in the spontaneous depolarization of sinoatrial node, and its cell connection plays an important role to achieve the conductivity and Synchronization of electrical interaction. Therefore, the researches of the ionic currents and related ion channels which are involved in the spontaneous depolarization and its cell connection seems more important.Objective To sum up the research advancement in ionic currents and related ion channels which are involved in the sinoatrial node spontaneous depolarization and its cell connection.Retrieval strategy The relevant articles published between July 1979 and March 2010 were searched for in Pub Med database by researcher of this article with the key words of "ion channel, sinoatrial node" or "connexin, sinoatrial node" in English.643 articles were selected and reviewed by the inclusive criteria of:①articles closely related with the ionic currents and related ion channels which are involved in the sinoatrial node spontaneous depolarization and its cell connection;②the late articles and articles in authority journals in the same field.Literature evaluation The main sources of literatures were randomized clinical trial (RCT) on the ionic currents and related ion channels which are involved in the sino atrial node spontaneous depolarization and its cell connection. Among 43 selected articles,5 were reviews, and others were elementary experimental studies.Data synthesis①Gap junction is the main connection in sinoatrial node, and the molecular basis of gap junction is connexin. Cx45 with poor conductivity is the main connexin in the sino atrial node tissue, Cx43 with high conductivity is negative between P-P,P-T cells, but positive between T-atrial cells. From the central of sino atrial node to crista terminalis, Cx43 express from nothing to weakly to strongly. Cx43 express in the edge of the crista terminalis, there is a transitive region between sinoatrial node periphery and crista terminalis, where Cx43 and Cx45 expression at the same time.②Because of the special distribution of the Cx45 with low conductivity and Cx43 with high conductivity in sinoatrial node, the conductivity is gradually increased from the central of the sinoatrial node to the periphery, and it is the lowest in the central. Thanks to the protection of the Cx45 with low conductivity, the pacemaker cells in the central of the sinoatrial node can not be inhibited from the atrial cells.③The spontaneous depolarization in the sinoatrial node is caused by an net inward current increased with time, and it is mainly composed of one kind of outward current and two kinds of inward currents:1 The delayed rectifier current Ik1 channel lose the activity gradually and the outflow of K+ reduce gradually.2 A gradually enhanced inward current If; 3 The activation of calcium channel and calcium influx.Conclusion A variety of ion channels are involved in the spontaneous depolarization of sino atrial node, and its cell connection plays an important role to achieve the conductivity and Synchronization of electrical interaction.Part II Biological Pacemaker for treatment of sick sinus syndromeBackground Sick sinus syndrome refers to the lesions and dysfunction of the sinus node and surrounding tissue which caused a series of arrhythmia. Traditional treatment is to implanted electronic pacemakers, bio-pacemaker has opened up a whole new field for sick sinus syndrome along with the development of molecular biology techniques. Bio-pacemaker refers to using Cell Molecular Biology and related technologies to repair or replace the damaged self-rhythm points or special conduction system so that the heart pacemaker and conduction function can resume, including bio-pacemaker with the use of genes, bio-pacemaker with the use of cells and bio-pacemaker with the use of genes and stem cells.Objective To sum up the research advancement in constructing biological pacemaker with molecular biology techniques.Retrieval strategy The relevant articles published between July 1979 and March 2009 were searched for in Pub Med database by researcher of this article with the key words of "biological pacemaker" and "stem cell","biological pacemaker" and "gene" in English.85 articles were selected and reviewed by the inclusive criteria of:①articles closely related with the construction of biological pacemaker;②the late articles and articles in authority journals in the same field.Literature evaluation The main sources of literatures were randomized clinical trial (RCT) on biological pacemaker by gene or stem cells. Among 40 selected articles,8 were reviews, and others were elementary experimental studies.Data synthesis①Bio-pacemaker refers to using Cell Molecular Biology and related technologies to repair or replace the damaged self-rhythm points or special conduction system so that the heart pacemaker and conduction function can resume, including bio-pacemaker with the use of genes, bio-pacemaker with the use of cells and bio-pacemaker with the use of genes and stem cells.②The studies of gene therapy have focused on three areas:1 Increasing the P2 receptor in myocardial cell membrane through transfect the cloning gene of theβ2 receptor, to increase the cardiac response to endogenous and exogenous adrenaline and increase the heart rate; 2 Mutating the gene of Kir2 which encode potassium channels Ik1 to reduce the hyperpolarization current, it would enable the non-pacemaker generate the independent action potential activity as the pacemaker; 3 Transfect the gene of hyperpolarization-activated cyclic nucleotide-gated channel(HCN) which encode the pacemaker current If, it would induce the ventricular cells to beat independently.③Stem cell therapy is to induce stem cells (including the embryonic stem cells, mesenchymal stem cells, etc.) to differentiate into a functional pacemaker and conduction cells, then transplant then into the heart to reconstruction the pacemaker and conduction system.④Bio-pacemaker with the use of genes and stem cells is to load the genes which encode the pacemaker current channel into the stem cells, that is building a genetically modified stem cell.Conclusion Constructing biological pacemaker by gene or stem cells has become an optimal approach to treating the sick sinus syndrome.