Distribution of Atrial and Nodal Cells Within the Rabbit Sinoatrial Node

Verheijck, E. E.; Wessels, Andy; Ginneken, A. C. G. Van; Bourier, Jan; Markman, Marry; Vermeulen, Jacqueline L.M.; Bakker, Jacques M.T. de; Lamers, Wouter H.; Opthof, Tobias; Bouman, L. N.

doi:10.1161/01.cir.97.16.1623

Cited by 133 publications

(132 citation statements)

References 42 publications

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“…The contractile system was extremely poorly developed and was less axially oriented than in atrium cells (33). It has been described previously that the majority of rabbit SAN cells, but not atrial myocytes, reacted with anti-neurofilament NF-L antibody (34). We found that a large proportion of spindle-like SAN cells in our preparation reacted with anti-neurofilament NF-M antibody iC8.…”

Section: Hcn1 Expression In Sinoatrial Nodementioning

confidence: 43%

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Moroni¹,

Gorza²,

Beltrame³

et al. 2001

Journal of Biological Chemistry

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The pacemaker current I f of the sinoatrial node (SAN) is a major determinant of cardiac diastolic depolarization and plays a key role in controlling heart rate and its modulation by neurotransmitters. Substantial expression of two different mRNAs (HCN4, HCN1) of the family of pacemaker channels (HCN) is found in rabbit SAN, suggesting that the native channels may be formed by different isoforms. Here we report the cloning and heterologous expression of HCN1 from rabbit SAN and its specific localization in pacemaker myocytes. rbHCN1 is an 822-amino acid protein that, in human embryonic kidney 293 cells, displayed electrophysiological properties similar to those of I f , suggesting that HCN1 can form a pacemaker channel. The presence of HCN1 in the SAN myocytes but not in nearby heart regions, and the electrophysiological properties of the channels formed by it, suggest that HCN1 plays a central and specific role in the formation of SAN pacemaker currents.

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Section: Hcn1 Expression In Sinoatrial Nodementioning

confidence: 43%

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Moroni¹,

Gorza²,

Beltrame³

et al. 2001

Journal of Biological Chemistry

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“…The right atrium (RA) preparation, including the SAN and crista terminalis, was isolated and immersed in normal Tyrode's solution consisting of 137 mM NaCl, 4 mM KCl, 15 mM NaHCO 3 , 0.5 mM NaH 2 PO 4 , 0.5 mM MgCl 2 , 2.7 mM CaCl 2 and 11 mM dextrose. The SAN was identified as a whitish endocardial region near the junction of the RA-free wall and atrial appendage near the crista terminalis (21). release inhibitor (ryanodine, 0.3 or 3 µM), sodium current inhibitor [tetrodotoxin (TTX), 1, 3 or 10 µM in 0.01% acetic acid) and late sodium current inhibitor (ranolazine, 10 µM).…”

Section: Methodsmentioning

confidence: 99%

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Chang

Chuang

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. 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 Ca 2+ 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.

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“…n the pages of Circulation, Verheijck et al 1 proposed a radical reinterpretation of the makeup of the sinoatrial (SA) node: the mosaic model. The SA node is a spatially extended structure (Ϸ4ϫ5 mm in rabbit).…”

mentioning

confidence: 99%

Gradient Model Versus Mosaic Model of the Sinoatrial Node

2001

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Background-A radical reinterpretation (mosaic model) of the makeup of the sinoatrial (SA) node has been proposed to explain the characteristic regional differences in electrical activity between the periphery and center of the SA node. According to the mosaic model, the differences result from a change in the mix of atrial cells and uniform SA node cells from periphery to center, whereas according to the alternative gradient model, there are no atrial cells within the functional SA node, and the differences result from a change in the intrinsic properties of SA node cells from periphery to center. Methods and Results-A mosaic model of peripheral and central tissue has been constructed computationally by use of a coupled ordinary differential equation network (CODE) in a 2D lattice (20ϫ20), with each node of the lattice designated randomly as an atrial cell or SA node cell (in correct proportions for periphery and center). The mosaic model fails to predict the characteristic differences in action potential rate and shape between the periphery and center, whereas the existing gradient model can do so. Conclusions-The mosaic model of the SA node is untenable, and the SA node is adequately described by the gradient model. (Circulation. 2001;103:584-588.)

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Distribution of Atrial and Nodal Cells Within the Rabbit Sinoatrial Node

Cited by 133 publications

References 42 publications

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 Is a Molecular Determinant of the Cardiac Pacemaker Current I f

Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Gradient Model Versus Mosaic Model of the Sinoatrial Node

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