Sophisticated Architecture is Required for the Sinoatrial Node to Perform Its Normal Pacemaker Function

Boyett, Mark R.; Dobrzynski, Halina; Lancaster, Matthew K.; Jones, Sandra A.; Honjo, Haruo; Kodama, Itsuo

doi:10.1046/j.1540-8167.2003.02307.x

Cited by 55 publications

(48 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10 In a recent study of rabbit SAN explants, using in situ dye transfer, gap Figure 1 Schema of connexin43-expressing lentiviral vector constructs. The cDNA for the rat connexin43-GFP (Cx43GFP) fusion gene and a 21-bp Cx43 deletion mutant (Cx43D7) were sub-cloned into the third-generation lentiviral vector construct pRRLsin18.cPPT.CMV.…”

mentioning

confidence: 99%

“…The structural organization of fibroblasts within the SAN and the ordered pattern of connexin expression in these cells strongly implicate an important electrophysiological function of heterologous coupling. 10,11 Electrical impulse generation and conduction occur in the SAN and both have dependence on membrane excitability. It is likely, therefore, that fibroblasts, via heterologous coupling, exert a modulatory effect on these processes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Fibroblasts modulate cardiomyocyte excitability: implications for cardiac gene therapy

et al. 2006

View full text Add to dashboard Cite

In an earlier study exploring the potential of gene transfer to repair myocardial conduction defects, we observed that myotubes, generated by forced expression of MyoD, exhibit reduced excitability when also modified to express connexin43 (Cx43). We hypothesized that this effect was caused by gap junction-mediated coupling between myotubes and the underlying fibroblast feeder layer. This intriguing possibility has important implications for ongoing efforts to develop strategies for repairing myocardial conduction defects by gene transfer, and also provides novel insights into the electrophysiological function of naturally occurring heterologous cell coupling within the heart. Although a conductive function for fibroblasts through heterologous coupling has previously been reported, the current study provides novel evidence that fibroblasts can modulate cardiomyocyte excitability in a Cx43-dependent manner. In a co-culture study system, neonatal rat cardiomyocytes were grown on monolayers of mouse fibroblasts with genetically altered Cx43 expression and the effect on intrinsic beat frequency examined. Cardiomyocytes grown on wild-type (WT) fibroblasts expressing native levels of Cx43 beat significantly slower than cells grown on fibroblasts devoid of this molecule (germline knockout) or with dominant-negative functional suppression. Expression of Cx43 in fibroblasts from Cx43 knockout mice restored cardiomyocyte beat frequency, to rates comparable with those observed in co-culture with WT fibroblasts.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Fibroblasts modulate cardiomyocyte excitability: implications for cardiac gene therapy

et al. 2006

View full text Add to dashboard Cite

show abstract

“…We first isolated K ATP currents in single SAN cells and find that only approximately half the cells contain currents [98]. This is not surprising given the heterogeneous electrophysiological nature of the SAN [100]. Importantly this number of cells was significantly reduced in cKO mice [98].…”

Section: Katp Channels Underlie Repolarising Currents In the Sa Nodementioning

confidence: 99%

Potassium channels in the sinoatrial node and their role in heart rate control

Aziz

Tinker

2018

Channels

View full text Add to dashboard Cite

Potassium currents determine the resting membrane potential and govern repolarisation in cardiac myocytes. Here, we review the various currents in the sinoatrial node focussing on their molecular and cellular properties and their role in pacemaking and heart rate control. We also describe how our recent finding of a novel ATP-sensitive potassium channel population in these cells fits into this picture.

show abstract

“…Confocal microscopic analysis was performed on the specimens. We used the immunohistochemical definition of the adult SAN of Boyett et al [9][10][11], i.e., a heterogeneous population of automatic cells in the atria near the crista-terminalis with its core positive for Cx45 and HCN4 and periphery positive for both Cx45 and Cx43. Immunostained sections were then examined for the specificity of marker expression with respect to the CCS under an Axioplane LSM510 (Carl Zeiss) confocal microscope.…”

Section: Staining and Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…Taken together, the SAN can be defined as a heterogeneous population of automatic cells in the atria near the crista-terminalis with its core positive for Cx45 and HCN4 and periphery positive for both Cx45 and Cx43 [9][10][11]. Cx40, Cx43, Cx45 and Cx30.2 are considered the primary connexins of the heart and have specific compartmentalized expression pattern both in the conduction system and in the myocardium.…”

Section: Introductionmentioning

confidence: 99%

Characterization of sinoatrial node in four conduction system marker mice

Viswanathan

Burch

Fishman

et al. 2007

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

The specialized cardiac conduction system (CCS) consists of the sinoatrial node (SAN) and the atrioventricular (AV) conduction system (AVCS), which includes proximal (AV node, bundle of His and bundle branches) and distal (Purkinje fibers) components. In four CCS marker mice [two transgenic (cGATA6|lacZ, CCS|lacZ) and two targeted gene knock-in (minK|lacZ, Hop|lacZ)] the expression of the lacZ gene (β-gal) has been reported to mark portions of the proximal and distal AVCS; the expression of this marker in the adult SAN is unknown. The primary objective of this study was to analyze the utility of these marker mice in the identification of the SAN. Intercaval and interventricular septal regions, containing all the components of the CCS, were freshly dissected from adult mice based on the anatomical landmarks and sectioned. Immunohistochemical characterization was performed with SAN markers (Cx45, HCN4), compared to the reporter expression (β-gal) and markers of the working myocardium (Cx40 and Cx43). In all four of the CCS marker mice, we found that β-gal expression is consistently observed in the proximal and distal AVCS. However, the presence of lacZ gene expression in the working myocardium outside the CCS and/or the absence of this reporter expression in the SAN prevent the effective use of these mice to identify the SAN, leading us to conclude that none of the four CCS marker mice we studied specifically mark the SAN.

show abstract

Sophisticated Architecture is Required for the Sinoatrial Node to Perform Its Normal Pacemaker Function

Cited by 55 publications

References 8 publications

Fibroblasts modulate cardiomyocyte excitability: implications for cardiac gene therapy

Fibroblasts modulate cardiomyocyte excitability: implications for cardiac gene therapy

Potassium channels in the sinoatrial node and their role in heart rate control

Characterization of sinoatrial node in four conduction system marker mice

Contact Info

Product

Resources

About