2006
DOI: 10.1016/j.cardiores.2006.07.026
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Abstract: The widespread distribution of HCN4 can explain the widespread location of the leading pacemaker site during sinus rhythm, the extensive region of tissue that has to be ablated to stop sinus rhythm, and the widespread distribution of ectopic foci responsible for atrial tachycardia.

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Cited by 95 publications
(83 citation statements)
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References 42 publications
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“…Hierarchy within the pacemaker complex is primarily based on a different ionic channel and Ca 2ϩ -handling gene repertoire in the leading SAN pacemaker and secondary pacemakers (21,24,34). The different expression patterns of the genes throughout the pacemaker complex result in multiple pacemaker cell types with various intrinsic rates modulated by the nonuniform distribution of adrenergic and cholinergic receptors (3,22,30 (20).…”
Section: Discussionmentioning
confidence: 99%
“…Hierarchy within the pacemaker complex is primarily based on a different ionic channel and Ca 2ϩ -handling gene repertoire in the leading SAN pacemaker and secondary pacemakers (21,24,34). The different expression patterns of the genes throughout the pacemaker complex result in multiple pacemaker cell types with various intrinsic rates modulated by the nonuniform distribution of adrenergic and cholinergic receptors (3,22,30 (20).…”
Section: Discussionmentioning
confidence: 99%
“…Subsequently, the SAN is identified as a structure comprising an Nkx2-5 − head region and an Nkx2-5 + sinoatrial (SA) junction or tail region (Liang et al, 2013;Liu et al, 2007;Wiese et al, 2009;Yamamoto et al, 2006), suggesting that the development of these two distinct SAN domains (Nkx2-5 + versus Nkx2-5 − ) is regulated by different mechanisms. The SAN is characterized by the expression of Hcn4, Tbx3, Isl1 and Shox2, but is negative for Cx40 (Gja5) and Nppa (Munshi, 2012).…”
Section: Introductionmentioning
confidence: 99%
“…Cx40, the most abundant connexin in the atria, is not present in the SAN [9][10][11]. Using this approach to identify the SAN in adult CCS marker mice, we found that a reporter gene that is consistently expressed in the proximal and distal AVCS is not specifically or consistently expressed in the SAN.…”
Section: Discussionmentioning
confidence: 94%
“…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%
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