Connexin hemichannel mediated ephaptic inhibition in the retina

Klaassen, Lauw J.; Fahrenfort, Iris; Kamermans, Maarten

doi:10.1016/j.brainres.2012.04.059

Cited by 29 publications

(29 citation statements)

References 60 publications

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“…Ephaptic coupling has been observed in neural (Anastassiou et al, 2011; Bokil et al, 2001; Chan et al, 1988; Faber and Korn, 1989; Jefferys, 1995; Su et al, 2012; Voronin, 2000), and other (Klaassen et al, 2012; Young, 2007) tissues, and has long been hypothesized to occur in the heart (Mori et al, 2008; Hichri et al, 2018; Kucera et al, 2002; Lin and Keener, 2013; Sperelakis, 2002). Early work on ephaptic coupling in the heart was motivated by the fact that GJs, which are abundant in mammalian hearts, are over two orders of magnitude less frequent in other chordates, especially birds (Martínez-Palomo and Mendez, 1971; Shibata and Yamamoto, 1979).…”

Section: Discussionmentioning

confidence: 99%

The adhesion function of the sodium channel beta subunit (β1) contributes to cardiac action potential propagation

Veeraraghavan

Hoeker

Alvarez-Laviada

et al. 2018

eLife

173

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Computational modeling indicates that cardiac conduction may involve ephaptic coupling – intercellular communication involving electrochemical signaling across narrow extracellular clefts between cardiomyocytes. We hypothesized that β1(SCN1B) –mediated adhesion scaffolds trans-activating NaV1.5 (SCN5A) channels within narrow (<30 nm) perinexal clefts adjacent to gap junctions (GJs), facilitating ephaptic coupling. Super-resolution imaging indicated preferential β1 localization at the perinexus, where it co-locates with NaV1.5. Smart patch clamp (SPC) indicated greater sodium current density (INa) at perinexi, relative to non-junctional sites. A novel, rationally designed peptide, βadp1, potently and selectively inhibited β1-mediated adhesion, in electric cell-substrate impedance sensing studies. βadp1 significantly widened perinexi in guinea pig ventricles, and selectively reduced perinexal INa, but not whole cell INa, in myocyte monolayers. In optical mapping studies, βadp1 precipitated arrhythmogenic conduction slowing. In summary, β1-mediated adhesion at the perinexus facilitates action potential propagation between cardiomyocytes, and may represent a novel target for anti-arrhythmic therapies.

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Section: Discussionmentioning

confidence: 99%

The adhesion function of the sodium channel beta subunit (β1) contributes to cardiac action potential propagation

Veeraraghavan

Hoeker

Alvarez-Laviada

et al. 2018

eLife

173

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“…Because Cx46 is a phosphoprotein, an involvement of guanylyl cyclase and PKG in the effect of CORM-2 is possible. However, pre-incubation for 45 min with 2 M KT5823 (a specific PKG inhibitor) or 50 M ODQ (1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, a specific guanylyl cyclase inhibitor) (27,28) did not affect the current inhibition induced by 100 M CORM-2 (Fig. 5A).…”

Section: Corms Inhibits Cx46 Hemichannel Currents-becausementioning

confidence: 98%

“…Hemichannels (HCs) 2 are hexamers of connexins thought to be normally closed, preventing cell losses of important metabolites such as ATP and glutathione, as well as massive entry of Ca 2ϩ (1,2). However, recent studies show that HCs undergo brief openings under physiological conditions (1,3); HC opening has been observed in ephaptic communication in the vertebrate retina (4), during the spread of Ca 2ϩ waves (5), memory consolidation in the amygdala (6), and neurotransmitter release (7). It is also known that HCs with high activity (leaky HCs) are observed in several diseases where it contributes to cell damage or death (8 -11).…”

mentioning

confidence: 99%

Carbon Monoxide (CO) Is a Novel Inhibitor of Connexin Hemichannels

León-Paravic

Figueroa

Guzmán

et al. 2014

Journal of Biological Chemistry

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“…In fish retina, HCs and Panx channels have been shown to contribute to a very fast ephaptic and a relatively slow proton-mediated mechanism, respectively (see Fig. 5b for more detailed information concerning the signaling mechanisms) [158][159][160][161][162]. HC/ Panx1 channel-mediated ephaptic transmission was also recently demonstrated in the mouse retina, albeit it is not completely clear whether it involves HCs and/or Panx1 channels [30,163].…”

Section: General Concepts Of Connexin and Pannexin Signalingmentioning

confidence: 99%

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Decrock

Bock

Wang

et al. 2015

Cell. Mol. Life Sci.

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The central nervous system (CNS) is composed of a highly heterogeneous population of cells. Dynamic interactions between different compartments (neuronal, glial, and vascular systems) drive CNS function and allow to integrate and process information as well as to respond accordingly. Communication within this functional unit, coined the neuro-glio-vascular unit (NGVU), typically relies on two main mechanisms: direct cell-cell coupling via gap junction channels (GJCs) and paracrine communication via the extracellular compartment, two routes to which channels composed of transmembrane connexin (Cx) or pannexin (Panx) proteins can contribute. Multiple isoforms of both protein families are present in the CNS and each CNS cell type is characterized by a unique Cx/Panx portfolio. Over the last two decades, research has uncovered a multilevel platform via which Cxs and Panxs can influence different cellular functions within a tissue: (1) Cx GJCs enable a direct cell-cell communication of small molecules, (2) Cx hemichannels and Panx channels can contribute to autocrine/paracrine signaling pathways, and (3) different structural domains of these proteins allow for channel-independent functions, such as cell-cell adhesion, interactions with the cytoskeleton, and the activation of intracellular signaling pathways. In this paper, we discuss current knowledge on their multifaceted contribution to brain development and to specific processes in the NGVU, including synaptic transmission and plasticity, glial signaling, vasomotor control, and blood-brain barrier integrity in the mature CNS. By highlighting both physiological and pathological conditions, it becomes evident that Cxs and Panxs can play a dual role in the CNS and that an accurate fine-tuning of each signaling mechanism is crucial for normal CNS physiology.

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Connexin hemichannel mediated ephaptic inhibition in the retina

Cited by 29 publications

References 60 publications

The adhesion function of the sodium channel beta subunit (β1) contributes to cardiac action potential propagation

The adhesion function of the sodium channel beta subunit (β1) contributes to cardiac action potential propagation

Carbon Monoxide (CO) Is a Novel Inhibitor of Connexin Hemichannels

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

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