Similar Datasets
Project description:ObjectivesThis study sought to investigate the shift of leading pacemaker locations in healthy and failing mammalian hearts over the entire range of physiological heart rates (HRs), and to molecularly characterize spatial regions of spontaneous activity.BackgroundA normal heartbeat originates as an action potential in a group of pacemaker cells known as the sinoatrial node (SAN), located near the superior vena cava. HRs and the anatomical site of origin of pacemaker activity in the adult heart are known to dynamically change in response to various physiological inputs, yet the mechanism of this pacemaker shift is not well understood.MethodsOptical mapping was applied to ex vivo rat and human isolated right atrial tissues, and HRs were modulated with acetylcholine and isoproterenol. RNA sequencing was performed on tissue areas that elicited spontaneous activity, and comparisons were made to neighboring myocardial tissues.ResultsFunctional and molecular evidence identified and confirmed the presence of 2 competing right atrial pacemakers localized near the superior vena cava and the inferior vena cava-the superior SAN (sSAN) and inferior SAN (iSAN), respectively-which preferentially control the fast and slow HRs. Both of these regions were evident in non-failing rat and human hearts and maintained spontaneous activity in the rat heart when physically separated from one another. Molecular analysis of these 2 pacemaker regions revealed unique but similar transcriptional profiles, suggesting iSAN dominance when the sSAN is silent.ConclusionsThe presence of 2 spatially distinct dominant pacemakers, sSAN and iSAN, in the mammalian heart clarifies previous identification of migrating pacemakers and corresponding changes in P-wave morphology in mammalian species.
| S-EPMC7770336 | biostudies-literature
Project description:We report the application of RNA sequencing technology for high-throughput profiling of regionally separated sinoatrial nodal tissues from rat hearts. We find that both the superior and inferior regions of these sinoatrial nodal tissues (termed sSAN and iSAN, respectively) possess statistically comparable levels of cardiac ion channels, receptors, neural proteins, and transcription factors. This study provides new insights into regional molecular expression of pacemaking tissue in the right atria.
2021-04-26 | GSE149542 | GEO
Project description:We report the application of RNA sequencing technology for high-throughput profiling of regionally separated sinoatrial nodal tissues from human hearts. We find that both the superior and inferior regions of these sinoatrial nodal tissues (termed sSAN and iSAN, respectively) possess statistically comparable levels of cardiac ion channels, receptors, neural proteins, and transcription factors. This study provides new insights into regional molecular expression of pacemaking tissue in the right atria.
2021-04-26 | GSE149541 | GEO
Project description:Evidence of superior and inferior sinoatrial nodes in the mammalian heart
| PRJNA629003 | ENA
Project description:Evidence of superior and inferior sinoatrial nodes in the mammalian heart [Rat]
| PRJNA629005 | ENA
Project description:Evidence of superior and inferior sinoatrial nodes in the mammalian heart [Human]
| PRJNA629001 | ENA
Project description:Objectives: This study aimed to determine the transcriptional basis of functional silencing of one of the two dominant pacemakers in failing rat hearts. Background: Recently, our laboratory presented functional and molecular evidence for the presence of two competing sinoatrial node (SAN) pacemakers in the healthy human and rat hearts. Anatomically localized near the superior vena cava and inferior vena cava, the superior and inferior SANs (sSAN and iSAN), respectively, preferentially control fast and slow normal heart rates. However, only one dominant pacemaker, primarily sSAN, was functional in the failing rat heart with hypertrophic cardiomyopathy. Methods: Ascending aortic constriction was performed on 1-week-old male Sprague-Dawley rat pups to induce left ventricular hypertrophy and heart failure. The dominant pacemaker was anatomically mapped in adult (8-12 weeks old) healthy and failing rat hearts using optical mapping in isolated right atrial tissue preparations. RNA sequencing was used to identify regional sSAN/iSAN gene expression differences between healthy and failing rat hearts. Results: In all failing rat hearts optically mapped in this study (n=4), only the sSAN pacemaker was functional, while the iSAN was silent. Compared to healthy rat hearts, a total of 3,640 genes were downregulated and 4,518 genes were upregulated in failing rat hearts. The functional quiescence of the iSAN in these failing rat hearts may be explained by their downregulation of sodium, potassium, and calcium ion channels as well as their downregulation of certain structural genes, including ankyrin, titin, and myosin heavy chain. Moreover, the iSAN showed predominant downregulation of several key transcription factors such as TBX5, TBX3, SHOX2, and SMAD9. Conclusions: Pressure-overload-induced heart failure resulted in significant downregulation of critical transcription factors, ion channels, and structural transcripts of the iSAN, which could explain the functional silencing of the iSAN in failing rat hearts.
2022-05-17 | GSE201717 | GEO
Project description:The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 µM), a calmodulin kinase II inhibitor (KN-93; 0.3 or 3 µM), a sarcoplasmic reticulum Ca2+ release inhibitor (ryanodine; 0.3 or 3 µM), a sodium current inhibitor (tetrodotoxin; 1, 3 or 10 µM) and a late sodium current inhibitor (ranolazine; 10 µM). Western blot analysis was used to investigate the protein expression in SANs from normal rabbits and those with HF. Control SANs had a higher beating rate than SANs from rabbits with HF (2.3±0.1 vs. 1.5±0.1 Hz; P<0.001). Similarly, ivabradine (10 µM), KN-93 (3 µM), ranolazine (10 µM) and ryanodine (3 µM) decreased the beating rates of SANs in the control (n=6) and HF (n=6) groups. Ivabradine treatment resulted in a higher incidence of AP block in HF vs. control SANs (66.7 vs. 0%; P<0.05). Tetrodotoxin (1, 3 or 10 µM) decreased the beating rate to a higher extent in SANs from rabbits with HF than in those from control rabbits and induced a higher incidence of AP block (66.7 vs. 0%; P<0.05). Furthermore, SANs from rabbits with HF had higher protein levels of phospholamban (PLB) and lower levels of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, ryanodine receptor and phosphorylated PLB than control SANs. In conclusion, HF modulates electropharmacological responses in the SAN by channel regulation, which may result in SAN dysfunction.
| S-EPMC5348682 | biostudies-other
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-11-17 | E-GEOD-62389 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-04-06 | GSE196439 | GEO