Chamber-related Differences in Connexin Expression in the Human Heart

Vozzi, Cristina; Dupont, Emmanuel; Coppen, Steven R.; Yeh, Hung‐I; Severs, Nicholas J.

doi:10.1006/jmcc.1999.0937

Cited by 217 publications

(164 citation statements)

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“…26 The protein was loaded with an equal amount (20 mg) per lane for electrophoresis. After transfer to nitrocellulose, membranes were blocked and probed for 60 min with anti-Cx43 (1:250), anti-JNK (1:100; Santa Cruz Biotechnology), or anti-phospho-JNK (1:1000; Cell Signaling Technology).…”

Section: Immunoblottingmentioning

confidence: 99%

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Lin

Yeh

et al. 2005

Laboratory Investigation

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The effects of hypercholesterolemia on the myocardium per se include electrophysiological and mechanical alterations. Since gap junctions are essential in electromechanical coupling throughout the heart, we examined the correlation between the temporal expression of cardiac connexin 43 (Cx43), contractile function, and conduction velocity in cholesterol-fed rabbits. After a 12-week feeding period, serum cholesterol levels gradually increased (Po0.001). In contrast, expression of cardiomyocyte Cx43 protein progressively decreased (60% reduction at 12 weeks, Po0.001). Such a reduction was also demonstrated by immunoconfocal microscopy, which further showed redistribution of Cx43 gap junctions at the lateral cell membrane. The downregulation of Cx43 protein was associated with increased levels of Cx43 mRNA (3.5 -fold at 12 weeks, Po0.001) and phosphorylated c-Jun N-terminal kinase (three-fold at 12 weeks, P ¼ 0.001). Functionally, although fractional shortening of the left ventricle remained unchanged throughout the feeding protocol, the cholesterol-fed rabbits had a reduced cardiac cycle-dependent variation of integrated backscatters, a decreased mitral ring systolic velocity, and an increased modified Tei index (all Po0.001), all of which indicated impaired intrinsic myocardial contractility and attenuated ventricular systolic performance. In Langendorff-perfused hearts of cholesterol-fed rabbits, decreased conduction velocity was observed (Po0.005). Withdrawal of the cholesterol-enriched diet for 18 weeks restored the contractile parameters and Cx43 protein expression. These findings suggest that Cx43 is highly involved in the molecular mechanism of hypercholesterolemia-induced cardiac contractile dysfunction and dysrhythmias.

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Section: Immunoblottingmentioning

confidence: 99%

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Lin

Yeh

et al. 2005

Laboratory Investigation

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“…The most connexin heterogeneous tissue within the heart is atrial myocardium making it very difficult to sort out the effects of remodeling as described below. The atrium contains Cx40, Cx43, and Cx45 ( Figure 1) [43,45,46]. Cx40 is expressed in high levels, 2 to 3 fold higher in the right atrium than the left [46].…”

Section: Structure and Function Of Gap Junctionsmentioning

confidence: 99%

“…The atrium contains Cx40, Cx43, and Cx45 ( Figure 1) [43,45,46]. Cx40 is expressed in high levels, 2 to 3 fold higher in the right atrium than the left [46]. It has been shown that the normal Cx40 distribution may also be heterogeneous with areas containing large amounts of Cx40 adjacent to others containing minimal or no Cx40 although hetrogeneities have not been precisely quantified [47][48][49].…”

Section: Structure and Function Of Gap Junctionsmentioning

confidence: 99%

“…While there have been few studies of protein partners for Cx40, the amino acid sequence of the carboxyl terminal domain is suggestive of regulation by kinases and phosphatases (see below), thus altered interactions of connexins with regulatory proteins may also be involved in remodeling. Unlike Cx40, Cx43 is distributed homogeneously throughout the right and left atria and reaches levels similar to Cx40 in the right atrium [46]. Cx43 channels have a unitary conductance between that of Cx45 and Cx40 (~120 pS) and is also both voltage and pH dependent [42].…”

Section: Structure and Function Of Gap Junctionsmentioning

confidence: 99%

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Is there a role for remodeled connexins in AF? No simple answers

Duffy¹,

Wit²

2008

Journal of Molecular and Cellular Cardiology

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“…In the human heart, Cx43, Cx40 and Cx45 are co-expressed in distinctive combinations and relative quantities in different, functionally specialized subsets of myocytes [32].…”

Section: Introductionmentioning

confidence: 99%

Functional consequences of co-expressing connexin40 or connexin45 with connexin43 on intercellular electrical coupling

Thomas

Gray

Fry

et al. 2017

Biochemical and Biophysical Research Communications

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The functional characteristics of the co-expression of connexin43, connexin40, and connexin45 proteins in human myocardium are thought to play an important role in governing normal propagation of the cardiac electrical impulse and in generating the myocardial substrate for some arrhythmias and conduction disturbances.A rat liver epithelial cell line, that endogenously expresses connexin43, was used to induce also expression of connexin40 or connexin45 after stable transfection using an inducible ecdysone system. Electrical coupling was estimated from measurement of the input resistance of transfected cells using an intracellular microelectrode to inject current and record changes to membrane potential.However, varied expression of the transfected connexin40 or connexin45 did not change electrical coupling, although connexin43/40 co-expression led to better coupling than connexin43/45 co-expression. Quantification of endogenous connexin43 expression, at both mRNA and protein levels, showed that it was altered in a manner dependent on the transfected connexin isotype.The data using rat liver epithelial cells indicate an increased electrical coupling upon expression of connexin40 and connexin43 but decreased coupling with connexin45 and connexin43 co-expression.

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Chamber-related Differences in Connexin Expression in the Human Heart

Cited by 217 publications

References 0 publications

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Is there a role for remodeled connexins in AF? No simple answers

Functional consequences of co-expressing connexin40 or connexin45 with connexin43 on intercellular electrical coupling

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