1. Mechanoelectric feedback (MEF) in the heart is the process by which mechanical forces on the myocardium can change its electrical properties. Mechanoelectric feedback has been demonstrated in many animal models, ranging from isolated cells, through isolated hearts to whole animals. In humans, MEF has been demonstrated directly in both the atria and the ventricles. It seems likely that MEF provides either the trigger or the substrate for some types of clinically important arrhythmias. 2. Mechanoelectric feedback may arise because of the presence of stretch-sensitive (or mechano-sensitive) ion channels in the cell membrane of the cardiac myocytes. Two types have been demonstrated: (i) a non-specific cation channel (stretch-activated channel (SAC); conductance of approximately 25 pS); and (ii) a potassium channel with a conductance of approximately 100 pS. The gene coding for the SAC has not yet been identified. The gene for the potassium channel is likely to be TREK, a member of the tandem pore potassium channel gene family. We have recorded stretch-sensitive potassium channels in rat isolated myocytes that have the properties of TREK channels expressed in heterologous systems. 3. It has been shown that TREK mRNA is expressed heterogeneously in the rat ventricular wall, with 17-fold more expression in endocardial compared with epicardial cells. This difference is reflected in the TREK currents recorded from endocardial and epicardial cells using whole-cell patch-clamp techniques, although the difference in current density was less pronounced (approximately threefold). Consistent with this, we show here that when the ventricle is stretched by inflation of an intraventricular balloon in a Langendorff perfused rat isolated heart, action potential shortening was more pronounced in the endocardium (30% shortening at 40 mmHg) compared with that in the epicardium (10% shortening at the same pressure). 4. Computer models of the mechanics of the (pig) heart show pronounced spatial variations in strain in the myocardium with large transmural differences (in the left ventricle in particular) and also large differences between the base and apex of the ventricle. 5. The importance of MEF and the non-homogeneous gene expression and strain distribution for arrhythmias is discussed.
1. Many members of the tandem-pore K+ channel gene family have been reported to be present in cardiac cells. However, the pattern of gene expression of these channels in the heart is a matter of some dispute. 2. Here, we used reverse transcription and real-time quantitative polymerase chain reaction to investigate the pattern of gene expression of nine members of the tandem-pore K+ channel genes in adult and embryonic rat heart. The genes (TWIK-1, TWIK-2, TASK-1, TASK-2, TASK-3, TREK-1, TREK-2, TRAAK and KCNK6) were quantified, relative to glyceraldehyde-3-phosphate dehydrogenase (GADPH), in all four chambers of adult rat hearts and in the ventricles of embryonic rat hearts. 3. All these genes were detected in at least one chamber of the heart, with a predominance of TWIK-2, TASK-1 and TREK-1 expression. The expression of TWIK-2 was higher in the right atrium than in other cardiac chambers, TASK-1 was expressed more in atria than in ventricles and TREK-1 was highly expressed in the right ventricle. 4. The expression levels of the three predominant genes in embryonic rat ventricle are much lower than their expression in adult rat ventricles. 5. The physiological implications of the differential gene expression of the tandem-pore K+ channels is discussed.
S229 279 Left atrial appendage thrombus during anticoagulation with rivaroxaban
myocytes of diabetic rabbits as indicated by increase in co-immunoprecipitation (co-ip) of p47 phox with p22 phox subunits of NADPH oxidase and in glutathionylation of endothelial nitric oxide synthase (eNOS) (58 ± 6%) known to uncouple eNOS. Diabetes reduced co-ip of  1 Na +-K + pump subunit with glutaredoxin 1 (Grx1) that reverses glutathionylation of proteins. Consistent with this, glutathionylation of the  1 subunit was increased (52 ± 9%) and electrogenic Na +-K + pump current measured in voltage-clamped myocytes was reduced (0.26 ± 0.04 vs 0.44 ± 0.04 pA/pF). Administration of CL (40 g/kg/h) had no effect on glucose or insulin levels but reduced lipid peroxidation. It also reduced p47 phox /p22 phox co-ip, reduced glutathionylation of eNOS (51 ± 1%) and  1 pump subunit (74 ± 13%), increased Grx1/ 1 pump subunit co-ip and increased Na +-K + pump current (0.6 ± 0.1 vs 0.26 ± 0.04 pA/pF). Diabetes induced molecular remodelling in an oxidative pathway that is determinant of the functionally important oxidative modification of Na +-K + pump. Reversal of these changes by  3 AR stimulation suggests that  3 AR agonists may have cardiovascular protective effects in diabetes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.