Connexin43 and Connexin45 Form Heteromeric Gap Junction Channels in Which Individual Components Determine Permeability and Regulation

Martı́nez, Agustı́n D.; Hayrapetyan, Volodya; Moreno, Alonso P.; Beyer, Eric C.

doi:10.1161/01.res.0000019580.64013.31

Cited by 151 publications

(155 citation statements)

References 39 publications

(94 reference statements)

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“…4D); thus, although these cells contained both proteins, Cx30.2 dominated this property. This is reminiscent of previous cases in which one connexin dominates the dye permeability or kinase sensitivity properties of mixed channels [14]. Similar to other connexin pairs that form heteromeric channels (e.g., Cx37/Cx43 and Cx43/Cx45; [2,14] Cx30.2 and Cx40 co-expression may result in new single channel conductances, since these cells did not contain distinct large channels as expected for Cx40 alone.…”

Section: Discussionsupporting

confidence: 55%

“…This is reminiscent of previous cases in which one connexin dominates the dye permeability or kinase sensitivity properties of mixed channels [14]. Similar to other connexin pairs that form heteromeric channels (e.g., Cx37/Cx43 and Cx43/Cx45; [2,14] Cx30.2 and Cx40 co-expression may result in new single channel conductances, since these cells did not contain distinct large channels as expected for Cx40 alone.Taken together with data regarding expression patterns of cardiac connexins, our new results suggest that co-expression of Cx30.2 with some of the other connexins may influence cardiac intercellular communication. Cx30.2 has been identified in the sinoatrial node, atrioventricular node, and atrioventricular bundle [11,12].…”

supporting

confidence: 55%

“…In most cell pairs, voltage-dependent gating was intermediate between that of either connexin alone. These intermediate properties might reflect formation of heteromeric channels, similar to the situation of some connexins that make heteromeric channels (eg, Cx37/Cx43 and Cx43/Cx45) [2,14]; alternatively, they might correspond to the aggregate of a mixture of channels formed exclusively of the two different connexins. In some cell pairs, gating was similar to that of Cx30.2 alone; this might best be explained by an imbalance in expression levels of the two connexins with Cx30.2 being much greater.…”

Section: Discussionmentioning

confidence: 92%

“…Expression of Cx30.2 in Xenopus oocytes or transfected cells has shown that this connexin forms functional channels with rather unique properties including a low sensitivity of gating to transjunctional voltage and a smaller unitary conductance than other connexins (~9 pS) [10,11]. Since we have been interested in the formation of heteromeric channels between connexins expressed in heart and its consequences mixing upon cardiac intercellular communication [13,14], we designed the current study to examine the possible heteromeric mixing of Cx30.2 with Cx40, Cx43, or Cx45. Cells were transiently or stably transfected with connexin DNA using lipofectamine (Invitrogen/GIBCO) [15].…”

mentioning

confidence: 99%

“…Samples were analyzed by immunoblotting. We have previously utilized this procedure to identify heteromeric interactions between connexins and demonstrated the specificity of this procedure [13,14,16,19] including a variety of "negative controls". When the supernatant from cells expressing only an untagged connexin was applied to the MicroBeads, no connexin protein was found in the eluate; all connexin protein was recovered in the "flow-through".…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 55%

supporting

confidence: 55%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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Gap Junctions

Churko

Laird

2011

Cellular Domains

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Electrophysiological In Vitro Study of Long‐Range Signal Transmission by Astrocytic Networks

Hastings,

Yu,

Huang

et al. 2023

Advanced Science

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Astrocytes are diverse brain cells that form large networks communicating via gap junctions and chemical transmitters. Despite recent advances, the functions of astrocytic networks in information processing in the brain are not fully understood. In culture, brain slices, and in vivo, astrocytes, and neurons grow in tight association, making it challenging to establish whether signals that spread within astrocytic networks communicate with neuronal groups at distant sites, or whether astrocytes solely respond to their local environments. A multi‐electrode array (MEA)‐based device called AstroMEA is designed to separate neuronal and astrocytic networks, thus allowing to study the transfer of chemical and/or electrical signals transmitted via astrocytic networks capable of changing neuronal electrical behavior. AstroMEA demonstrates that cortical astrocytic networks can induce a significant upregulation in the firing frequency of neurons in response to a theta‐burst charge‐balanced biphasic current stimulation (5 pulses of 100 Hz × 10 with 200 ms intervals, 2 s total duration) of a separate neuronal‐astrocytic group in the absence of direct neuronal contact. This result corroborates the view of astrocytic networks as a parallel mechanism of signal transmission in the brain that is separate from the neuronal connectome. Translationally, it highlights the importance of astrocytic network protection as a treatment target.

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Connexin43 and Connexin45 Form Heteromeric Gap Junction Channels in Which Individual Components Determine Permeability and Regulation

Cited by 151 publications

References 39 publications

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

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

Gap Junctions

Electrophysiological In Vitro Study of Long‐Range Signal Transmission by Astrocytic Networks

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