Distinct gap junction protein phenotypes in cardiac tissues with disparate conduction properties

Davis, Lloyd M.; Kanter, H L; Beyer, Eric C.; Saffitz, Jeffrey E.

doi:10.1016/0735-1097(94)90879-6

Cited by 171 publications

(108 citation statements)

References 35 publications

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“…It is of interest that studies of heart showed remarkable similarities to observations in brain (Davis et al, 1994;GarciaDorado et al, 2004). Bystander death is prominent in ischemic heart and was first observed in the myocardium (Garcia-Dorado et al, 1989;Ruiz-Meana et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

A Central Role of Connexin 43 in Hypoxic Preconditioning

Lin

Lou²,

Kang³

et al. 2008

J. Neurosci.

155

134

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Preconditioning is an endogenous mechanism in which a nonlethal exposure increases cellular resistance to subsequent additional severe injury. Here we show that connexin 43 (Cx43) plays a key role in protection afforded by preconditioning. Cx43 null mice were insensitive to hypoxic preconditioning, whereas wild-type littermate mice exhibited a significant reduction in infarct volume after occlusion of the middle cerebral artery. In cultures, Cx43-deficient cells responded to preconditioning only after exogenous expression of Cx43, and protection was attenuated by small interference RNA or by channel blockers. Our observations indicate that preconditioning reduced degradation of Cx43, resulting in a marked increase in the number of plasma membrane Cx43 hemichannels. Consequently, efflux of ATP through hemichannels led to accumulation of its catabolic product adenosine, a potent neuroprotective agent. Thus, adaptive modulation of Cx43 can offset environmental stress by adenosine-mediated elevation of cellular resistance.

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Section: Discussionmentioning

confidence: 99%

A Central Role of Connexin 43 in Hypoxic Preconditioning

Lin

Lou²,

Kang³

et al. 2008

J. Neurosci.

155

134

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“…[5,6]. Cx45 is detected in sinoatrial and atrioventricular nodes, atrioventricular bundle and branches [7,8]. …”

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confidence: 99%

Cx30.2 can form heteromeric gap junction channels with other cardiac connexins

Gemel

Lin

Collins

et al. 2008

Biochemical and Biophysical Research Communications

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Since most cells in the heart co-express multiple connexins, we studied the possible heteromeric interactions between connexin30.2 and connexin40, connexin43 or connexin45 in transfected cells. Double label immunofluorescence microscopy showed that connexin30.2 extensively co-localized with each co-expressed connexin at appositional membranes. When Triton X-100 solubilized connexons were affinity purified from co-expressing cells, connexin30.2 was isolated together with connexin40, connexin43, or connexin45. Co-expression of connexin30.2 with connexin40, connexin43, or connexin45 did not significantly reduce total junctional conductance. Gap junction channels in cells co-expressing connexin30.2 with connexin43 or connexin45 exhibited voltagedependent gating intermediate between that of either connexin alone. In contrast, connexin30.2 dominated the voltage dependence when co-expressed with connexin40. Our data suggest that connexin30.2 can form heteromers with the other cardiac connexins and that mixed channel formation will influence the gating properties of gap junctions in cardiac regions that co-express these connexins. Keywords Gap Junction; Intercellular Communication; ConnexinCurrent passage between cells in the heart is facilitated by intercellular channels clustered in gap junctions. These channels are formed by docking of two hemichannels (connexons) provided by the opposing cells. Each connexon is a hexamer of subunit proteins called connexins (Cx). As demonstrated in cells expressing individual connexins, each connexin can form channels by itself (homomeric/homotypic channels), and different connexins form channels with different conductance, permeability and gating properties [1]. In cells coexpressing different connexins, heteromeric channels (containing different connexins in the same connexon) can potentially be formed [2].Many studies have shown the presence of three well characterized connexin proteins in the heart, Cx40, Cx43, and Cx45. Cx43 is most abundant in atrial and ventricular myocytes and in Purkinje fibers [3,4]. Cx40 is expressed in atrial myocardium, atrioventricular bundle and ✉Address correspondence to: Eric C. Beyer, MD PhD, University of Chicago, Department of Pediatrics MC4060, 5841 S. Maryland Ave, Chicago, IL 60637-1470, TEL: 773-834-1498.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. [5,6]. Cx45 is detected in sinoatrial and atrioventricular nodes, atrioventricular bundle and branches [7,8]. NIH Public AccessRecently, another cardiac connexin, mouse Cx30.2 (human Cx31.9) was discovered [9][10][11]. Cx30.2 expression was ...

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“…Three different connexins have been identified in cardiac myocytes: Cx43, connexin45 (Cx45), and connexin40 (Cx40). 8 These cardiac connexins are expressed in different amounts and combinations in different regions of the heart. For example, ventricular myocytes express Cx43 and Cx45, whereas atrial myocytes express Cx43, Cx45, and Cx40.…”

Section: Intercellular Coupling At Gap Junctionsmentioning

confidence: 99%

Do Alterations in Intercellular Coupling Play a Role in Cardiac Contractile Dysfunction?

Saffitz

Yamada

1998

Circulation

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Myocardial stunning 1 and hibernation 2 have been subjects of intense laboratory and clinical investigations to elucidate mechanisms responsible for contractile dysfunction after transient ischemia or chronic hypoperfusion. Considerable evidence has implicated the generation of oxygen-derived free radicals and derangements in myocardial energy metabolism and excitation-contraction coupling as major contributors to the pathogenesis of myocardial stunning and hibernation.3,4 Despite enormous progress in this area, however, our understanding of the cellular pathophysiology of contractile dysfunction in ischemic heart disease remains incomplete.

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Distinct gap junction protein phenotypes in cardiac tissues with disparate conduction properties

Abstract: Although most cardiac gap junctions contain connexin40, connexin43 and connexin45, the relative amounts of each of these connexins vary considerably in cardiac tissues with different conduction properties.

Cited by 171 publications

References 35 publications

A Central Role of Connexin 43 in Hypoxic Preconditioning

A Central Role of Connexin 43 in Hypoxic Preconditioning

Cx30.2 can form heteromeric gap junction channels with other cardiac connexins

Do Alterations in Intercellular Coupling Play a Role in Cardiac Contractile Dysfunction?

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