Lysophosphatidylcholine metabolism and cardiac arrhythmias

The ability of exogenous lysophosphatidylcholine (LPC) to produce electrophysiological abnormalities in cardiac tissues and cardiac arrhythmias in isolated hearts has been well documented. In this study, the arrhythmogenic nature of LPC in the rat, rabbit, and guinea pig hearts was studied. The rat heart was found to be the most susceptible to LPC-induced arrhythmias, while the guinea pig heart was the least susceptible. Perfusion with labelled LPC revealed that the severity of arrhythmias correlates well with the amount of labelled LPC found in the microsomal membrane. The biochemical basis for the differences in the accumulation of LPC in the microsomal membrane of different animal species was investigated. Our results strongly indicate that the LPC level in the microsomal membrane may be regulated by the activity of microsomal lysophospholipase.     

Right or left ear reference changes the voltage of frontal and parietal somatosensory evoked potentials

Short-latency cortical somatosensory evoked potentials (SEPs) to left median nerve stimulation were recorded with either the left or right earlobe as reference. With a right earlobe reference the voltage of the parietal N20 and P27 was reduced while the voltage of the frontal P20 and N30 was enhanced. The effects were consistent, but their size varied with the SEP component considered and also among the subjects. Analysis of SEPs at different scalp sites and at either earlobe suggested that the ear contralateral to the side stimulated picked up transient potential differences, depending a.o. on side asymmetry and geometry of the neural generators as disclosed in topographic mapping. For example, the right ear potential can be shifted negatively by the right N20 field evoked by left median nerve stimulation. The changes involve the absolute potential values, but not the time features of the gradients of potential fields. Scalp current density (SCD) maps are not affected. The results are pertinent for current discussions about which reference to use and document the practical recommendation of recording short-latency cortical SEPs with a reference at the ear ipsilateral (not contralateral) to the side of stimulation.     

Brain-heart interactions and cardiac ventricular arrhythmias

A wide range of evidence implicates the brain as playing a significant role in ventricular arrhythmias and sudden cardiac death. The mechanism is thought to involve the intermediary of the autonomic nervous system. Here we briefly consider possible mechanisms by which central neural processing may modulate the myocardial electrophysiology and hence the arrhythmia substrate.     

Gene therapy in cardiac arrhythmias

Gene therapy has progressed from a dream to a bedside reality in quite a few human diseases. From its first application in adenosine deaminase deficiency, through the years, its application has evolved to vascular angiogenesis and cardiac arrhythmias. Gene based biological pacemakers using viral vectors or mesenchymal cells tested in animal models hold much promise. Induction of pacemaker activity within the left bundle branch can provide stable heart rates. Genetic modification of the AV node mimicking beta blockade can be therapeutic in the management of atrial fibrillation. G protein overexpression to modify the AV node also is experimental. Modification and expression of potassium channel genes altering the delayed rectifier potassium currents may permit better management of congenital long QT syndromes. Arrhythmias in a failing heart are due to abnormal calcium cycling. Potential targets for genetic modulation include the sarcoplasmic reticulum calcium pump, calsequestrin and sodium calcium exchanger. Lastly the ethical concerns need to be addressed.     

心肌细胞缝隙连接重塑与心律失常

缝隙连接是相邻心肌细胞间电、化学偶联的通道,亦是心室肌成为功能性合胞体的重要结构.心肌有缝隙连接蛋白(connexin,CX) 40、43与45的表达,心室肌主要表达CX43.CX43形成的缝隙连接大部分呈点状分布于闰盘部位,心肌细胞膜侧面分布极少.心肌缺血-再灌注、肥厚、衰竭、高胆同醇与糖尿病条件下,心肌细胞缝隙连接...     

Caveolae, ion channels and cardiac arrhythmias

Caveolae are specialized membrane microdomains enriched in cholesterol and sphingolipids which are present in multiple cell types including cardiomyocytes. Along with the essential scaffolding protein caveolin-3, a number of different ion channels and transporters have been localized to caveolae in cardiac myocytes including L-type Ca²⁺ channels (Ca_v1.2), Na⁺ channels (Na_v1.5), pacemaker channels (HCN4), Na⁺/Ca²⁺ exchanger (NCX1) and others. Closely associated with these channels are specific macromolecular signaling complexes that provide highly localized regulation of the channels. Mutations in the caveolin-3 gene (CAV3) have been linked with the congenital long QT syndrome (LQT9), and mutations in caveolar-localized ion channels may contribute to other inherited arrhythmias. Changes in the caveolar microdomain in acquired heart disease may also lead to dysregulation and dysfunction of ion channels, altering the risk of arrhythmias in conditions such as heart failure. This review highlights the existing evidence identifying and characterizing ion channels localized to caveolae in cardiomyocytes and their role in arrhythmogenesis.