Role of dual pacemaker mechanisms in sinoatrial node discharge

2000 ◽  
Vol 7 (2) ◽  
pp. 100-113 ◽  
Author(s):  
Hengtao Zhang ◽  
Mario Vassalle
Keyword(s):  
Sinoatrial Node

scholarly journals Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

2021 ◽  
Vol 22 (11) ◽  
pp. 5645
Author(s):  
Stefano Morotti ◽  
Haibo Ni ◽  
Colin H. Peters ◽  
Christian Rickert ◽  
Ameneh Asgari-Targhi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Membrane Potential ◽  
In Silico ◽  
Sinoatrial Node ◽  
In Silico Analysis ◽  
Ankyrin B ◽  
Deficient Mice ◽  
Silico Analysis ◽  
Bursting Activity

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.

scholarly journals The Role of the Calcium and the Voltage Clocks in Sinoatrial Node Dysfunction

2011 ◽  
Vol 52 (2) ◽  
pp. 211 ◽  
Author(s):  
Boyoung Joung ◽  
Peng-Sheng Chen ◽  
Shien-Fong Lin
Keyword(s):  
Sinoatrial Node ◽  
Sinoatrial Node Dysfunction

scholarly journals Distribution and Functional Role of Inositol 1,4,5- tris phosphate Receptors in Mouse Sinoatrial Node

2011 ◽  
Vol 109 (8) ◽  
pp. 848-857 ◽  
Author(s):  
Yue-Kun Ju ◽  
Jie Liu ◽  
Bon Hyang Lee ◽  
Donna Lai ◽  
Elizabeth A. Woodcock ◽  
...  
Keyword(s):  
Functional Role ◽  
Sinoatrial Node

scholarly journals Role of pacemaking current in cardiac nodes: Insights from a comparative study of sinoatrial node and atrioventricular node

2008 ◽  
Vol 96 (1-3) ◽  
pp. 294-304 ◽  
Author(s):  
Jie Liu ◽  
Penelope J. Noble ◽  
Guosheng Xiao ◽  
Mohamed Abdelrahman ◽  
Halina Dobrzynski ◽  
...  
Keyword(s):  
Comparative Study ◽  
Sinoatrial Node ◽  
Atrioventricular Node

scholarly journals Computational assessment of the functional role of sinoatrial node exit pathways in the human heart

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0183727 ◽  
Author(s):  
Sanjay R. Kharche ◽  
Edward Vigmond ◽  
Igor R. Efimov ◽  
Halina Dobrzynski
Keyword(s):  
Functional Role ◽  
Human Heart ◽  
Sinoatrial Node

scholarly journals Control of sinus venous valve and sinoatrial node development by endocardial NOTCH1

2019 ◽  
Vol 116 (8) ◽  
pp. 1473-1486
Author(s):  
Yidong Wang ◽  
Pengfei Lu ◽  
Liping Jiang ◽  
Bingruo Wu ◽  
Bin Zhou
Keyword(s):  
Potential Role ◽  
Sinoatrial Node ◽  
Notch Signalling ◽  
Growth Defect ◽  
Rhythmic Contraction ◽  
Venous Valve ◽  
T Box ◽  
Embryo Cultures ◽  
Node Development

Abstract Aims Sinus venous valve (SVV) and sinoatrial node (SAN) develop together at the sinoatrial junction during embryogenesis. SVV ensures unidirectional cardiac input and SAN generates sinus rhythmic contraction, respectively; both functions are essential for embryonic survival. We aim to reveal the potential role of endocardial NOTCH signalling in SVV and SAN formation. Methods and results We specifically deleted Notch1 in the endocardium using an Nfatc1Cre line. This deletion resulted in underdeveloped SVV and SAN, associated with reduced expression of T-box transcription factors, Tbx5 andTbx18, which are essential for the formation of SVV and SAN. The deletion also led to decreased expression of Wnt2 in myocardium of SVV and SAN. WNT2 treatment was able to rescue the growth defect of SVV and SAN resulted from the Notch1 deletion in whole embryo cultures. Furthermore, the Notch1 deletion reduced the expression of Nrg1 in the SVV myocardium and supplement of NRG1 restored the growth of SVV in cultured Notch1 knockout embryos. Conclusion Our findings support that endocardial NOTCH1 controls the development of SVV and SAN by coordinating myocardial WNT and NRG1 signalling functions.

Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat

1977 ◽  
Vol 55 (4) ◽  
pp. 813-820 ◽  
Author(s):  
Richard L. Hughson ◽  
John R. Sutton ◽  
J. Desmond Fitzgerald ◽  
Norman L. Jones
Keyword(s):  
Sinoatrial Node ◽  
Parasympathetic Nervous System ◽  
Control Group ◽  
Response Curves ◽  
Chronotropic Response ◽  
In Vitro Measurements ◽  
The Right

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose–response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.

A mathematical model of a rabbit sinoatrial node cell

1994 ◽  
Vol 266 (3) ◽  
pp. C832-C852 ◽  
Author(s):  
S. S. Demir ◽  
J. W. Clark ◽  
C. R. Murphey ◽  
W. R. Giles
Keyword(s):  
Mathematical Model ◽  
Sinoatrial Node ◽  
Surface Membrane ◽  
Recent Experimental Data ◽  
Pacemaker Cells ◽  
Diffusion Limited ◽  
Electrophysiological Responses ◽  
Sinoatrial Node Cell ◽  
Rabbit Sinoatrial Node

A mathematical model for the electrophysiological responses of a rabbit sinoatrial node cell that is based on whole cell recordings from enzymatically isolated single pacemaker cells at 37 degrees C has been developed. The ion channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface membrane (sarcolemma) are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins (calmodulin and troponin). Original features of this model include 1) new equations for the hyperpolarization-activated inward current, 2) assessment of the role of the transient-type Ca2+ current during pacemaker depolarization, 3) inclusion of an Na+ current based on recent experimental data, and 4) demonstration of the possible influence of pump and exchanger currents and background currents on the pacemaker rate. This model provides acceptable fits to voltage-clamp and action potential data and can be used to seek biophysically based explanations of the electrophysiological activity in the rabbit sinoatrial node cell.

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