Cardiac connexins and impulse propagation

Jansen, John A.; Veen, Toon A.B. van; Bakker, Jacques M.T. de; Rijen, Harold V.M. van

doi:10.1016/j.yjmcc.2009.08.018

Cited by 147 publications

(148 citation statements)

References 125 publications

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“…Histologically, this proliferative "pre-chamber myocardium" contains well-organized sarcomeres and developed endoplasmic reticulum. Molecularly, the extinction of Tbx3 leads to the appearance of "high conductance" proteins [11][12][13] , such as the connexins Cx40 and Cx43 [14] , and the replacement of the Land T-type Ca 2+ channels by the fast voltage-activated sodium channel Scn5a (Nav1.5) [15] . HCN4 expression is also strongly decreased in the working myocardium, as this tissue loses its intrinsic pacemaker activity [16][17][18] .…”

Section: Development Of the Human Cardiac Conduction Systemmentioning

confidence: 99%

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

et al. 2016

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The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cellderived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca 2+ -activated K + channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

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Section: Development Of the Human Cardiac Conduction Systemmentioning

confidence: 99%

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

et al. 2016

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“…Connexons are the hexamers of the membranespanning proteins called connexins. At present, >20 connexin genes have been identified in mice and humans (28). In the human heart, myocyte gap junctions are constructed mainly by 3 different connexin isoforms, connexin40, connexin43, and connexin45.…”

Section: Introductionmentioning

confidence: 99%

Connexin40 nonsense mutation in familial atrial fibrillation

Yang

Zhang²,

Wang³

et al. 2010

Int J Mol Med

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Abstract. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantial morbidity and mortality. Genetic variants play important roles in the pathogenesis of AF. However, AF is a genetically heterogeneous disorder, and the genetic determinants in most patients with AF remain to be identified. In this study, the entire coding region of the connexin40 gene, encoding the cardiac gap junction membrane channel protein ·5, was sequenced in 126 unrelated probands with familial AF. A novel heterozygous mutation, c.145C>T, in connexin40, was identified in a proband. The mutation was predicted to introduce a premature stop codon at amino acid position 49 (p.Q49X). This nonsense mutation was present in all the living relatives of the mutation carrier, co-segregating with AF in the family with a penetrance of 100%. However, it was absent in 200 ethnically matched unrelated control individuals. The findings suggest a pathogenic link between the compromised connexin40 function and familial AF, hence providing new insight into the molecular mechanisms involved in AF.

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“…At HH st 10, mRNAs for GJa1, GJa5 and GJa7, which encode for cardiac connexin 43 (Cx43), 40 (Cx40) and 45 (Cx45), respectively (Jansen et al, 2010;Teunissen, 2004), were detected at low levels just above background (Fig. 1G).…”

Section: Avj Myocytes Differentiate With Physiological Features Uniqumentioning

confidence: 99%

Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction

et al. 2014

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Efficient blood flow depends on two developmental processes that occur within the atrioventricular junction (AVJ) of the heart: conduction delay, which entrains sequential chamber contraction; and valve formation, which prevents retrograde fluid movement. Defects in either result in severe congenital heart disease; however, little is known about the interplay between these two crucial developmental processes. Here, we show that AVJ conduction delay is locally assigned by the morphogenetic events that initiate valve formation. Our data demonstrate that physical separation from endocardial-derived factors prevents AVJ myocardium from becoming fast conducting. Mechanistically, this physical separation is induced by myocardial-derived factors that support cardiac jelly deposition at the onset of valve formation. These data offer a novel paradigm for conduction patterning, whereby reciprocal myocardialendocardial interactions coordinate the processes of valve formation with establishment of conduction delay. This, in turn, synchronizes the electrophysiological and structural events necessary for the optimization of blood flow through the developing heart.

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Cardiac connexins and impulse propagation

Cited by 147 publications

References 125 publications

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

Connexin40 nonsense mutation in familial atrial fibrillation

Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction

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