Gap Junctions in the Cardiovascular System

Spray, David C.; Suadicani, Sylvia O.; Srinivas, Miduturu; Gutstein, David E.; Fishman, Glenn I.

doi:10.1002/cphy.cp020104

Cited by 7 publications

(5 citation statements)

References 274 publications

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“…Prominence analysis further highlights the importance of the different junction types of the IDs, which are targets in multiple types of cardiomyopathy (reviewed in Spray et al 2001; Wit and Janse 2001; Perriard et al 2003; Dhein 2006; Schulz et al 2007; Saffitz et al 2007). However, while each junction type displays unique functions, we and others have shown previously that these structures frequently present intertwined relationships, and the expression of their component genes is coordinately regulated (reviewed in Derangeon et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent gene regulatory networks of the heart rhythm

Iacobaş

Thomas

et al. 2009

Funct Integr Genomics

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Expression level, control, and intercoordination of 66 selected heart rhythm determinant (HRD) genes were compared in atria and ventricles of four male and four female adult mice. We found that genes encoding various adrenergic receptors, ankyrins, ion channels and transporters, connexins, cadherins, plakophilins, and other components of the intercalated discs form a complex network that is chamber dependent and differs between the two sexes. In addition, most HRD genes in atria had higher expression in males than in females, while in ventricles, expression levels were mostly higher in females than in males. Moreover, significant chamber differences were observed between the sexes, with higher expression in atria than ventricles for males and higher expression in ventricles than atria for females. We have ranked the selected genes according to their prominence (new concept) within the HRD gene web defined as extent of expression coordination with the other web genes and stability of expression. Interestingly, the prominence hierarchy was substantially different between the two sexes. Taken together, these findings indicate that the organizational principles of the heart rhythm transcriptome are sex dependent, with the newly introduced prominence analysis allowing identification of genes that are pivotal for the sexual dichotomy.

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Section: Discussionmentioning

confidence: 99%

Sex-dependent gene regulatory networks of the heart rhythm

Iacobaş

Thomas

et al. 2009

Funct Integr Genomics

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“…Studies on connexins exogenously expressed in Xenopus oocytes and in communication-deficient mammalian cells have established gating properties for gap junctions formed by a variety of connexins (Bukauskas and Verselis, 2004;Harris, 2001;Spray et al, 2001 for reviews). However, with a few notable exceptions, the most compelling data on the properties of unpaired connexons or hemichannels was initially derived from oocytes expressing Cx46 and, more recently, Cx50.…”

Section: Functional Properties Expected Of and Reported For Hemichannelsmentioning

confidence: 99%

“…It could still be argued that the lack of voltage dependence of nonjunctional currents induced in astrocytes and other Cx43-containing cells (Stout et al, 2002) represents the situation occurring under natural conditions. On the other hand, voltage dependence of gap junctions in mammalian cells endogenously expressing Cx43 tends to be very similar in transfectants and in Xenopus oocytes (Scemes et al, 2000;Spray et al, 2001), and it is rare for exogenous expression not to reproduce native channel properties (such as unitary conductance, see below).…”

Section: Caveatsmentioning

confidence: 99%

Functional connexin “hemichannels”: A critical appraisal

Spray

Ransom

2006

Glia

Self Cite

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"Hemichannels" are defined as the halves of gap junction channels (also termed connexons) that are contributed by one cell; "hemichannels" are considered to be functional if they are open in nonjunctional membranes in the absence of pairing with partners from adjacent cells. Several recent reviews have summarized the blossoming literature regarding functional "hemichannels", in some cases encyclopedically. However, most of these previous reviews have been written with the assumption that all data reporting "hemichannel" involvement really have studied phenomena in which connexons actually form the permeability or conductance pathway. In this review, we have taken a slightly different approach. We review the concept of "hemichannels", summarize properties that might be expected of half gap junctions and evaluate the extent to which the properties of presumptive "hemichannels" match expectations. Then we consider functions attributed to hemichannels, provide an overview of other channel types that might fulfill similar roles and provide sets of criteria that might be applied to verify involvement of connexin hemichannels in cell and tissue function. One firm conclusion is reached. The study of hemichannels is technically challenging and fraught with opportunities for misinterpretation, so that future studies must apply rigorous standards for detection of hemichannel expression and function. At the same time there are reasons to expect surprises, including the possibility that some time honored techniques for studying gap junctions may prove unsuitable for detecting hemichannels. We advise hemichannel researchers to proceed with caution and an open mind.

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“…Gap peptides (inhibitors of the connexin proteins that comprise gap junctions) nearly completely abolished EDHF dilation and SMC hyperpolarization while EC hyperpolarization was maintained. Rather than being a stagnant bridge between two cells, gap junctions are gated by many factors including pH, voltage and calcium (Spray et al, 2002). Recent studies suggest that cAMP enhances gap junction permeability (Abudara et al, 2000;Burghardt et al, 1995;van Rijen et al, 2000) and EDHFmediated dilations (Griffith et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Impaired cAMP signaling does not account for the attenuated EDHF-mediated dilations in female rat middle cerebral artery

Sokoya

You

2007

Brain Research

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Dilations to endothelium-derived hyperpolarizing factor (EDHF) are significantly attenuated in the middle cerebral artery (MCA) isolated from female compared to male rats. Since gap junctions appear to be involved in the EDHF pathway and cAMP has been shown to enhance gap junction permeability, we tested the hypothesis that elevation of cAMP would enhance EDHF-mediated dilations in female rat MCA. Vascular diameter was measured in perfused MCA segments using videomicroscopy in the presence and absence of IBMX, an inhibitor of cAMP phosphodiesterase. In the presence of L-NAME and indomethacin, dilation to 10(-4) M ATP was significantly reduced in females (48+/-12%) compared to males (92+/-2%). IBMX, an inhibitor of cAMP phosphodiesterase, had no significant effect on ATP-mediated dilations in both males and females. Basal cAMP levels were comparable in male and female MCAs (1.7 pmol/mg protein). Incubation with IBMX (2 x 10(-4) M) significantly elevated cAMP in both male (12.8 pmol/mg protein) and female (11.2 pmol/mg protein) MCAs. Our results demonstrate that reduced EDHF dilations in female rat MCA cannot be solely attributed to impaired cAMP signaling. Future studies will target other potential sites along the EDHF pathway in order to identify why EDHF dilations are reduced in the female compared to the male rat MCA.

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Gap Junctions in the Cardiovascular System

Cited by 7 publications

References 274 publications

Sex-dependent gene regulatory networks of the heart rhythm

Sex-dependent gene regulatory networks of the heart rhythm

Functional connexin “hemichannels”: A critical appraisal

Impaired cAMP signaling does not account for the attenuated EDHF-mediated dilations in female rat middle cerebral artery

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