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RyR2 regulates Cx43 hemichannel intracellular Ca2+-dependent activation in cardiomyocytes Universiteit Gent KU Leuven
Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice Vrije Universiteit Brussel Universiteit Gent
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement ...
Mechanisms underlying connexin hemichannel activation in disease Vrije Universiteit Brussel
Gap junctions and connexin hemichannels mediate intercellular and extracellular commu-nication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, ...
Glucocorticoid receptor in astrocytes regulates midbrain dopamine neurodegeneration through connexin hemichannel activity Universiteit Gent
Connexin targeting peptides as inhibitors of voltage- and intracellular Ca2+-triggered Cx43 hemichannel opening KU Leuven Universiteit Gent
Connexins form gap junctions that function as intercellular channels and hemichannels that form a conduit between the cytoplasm and extracellular fluid when open. Peptide inhibitors of connexin channels, especially those identical to defined connexin sequences, are interesting experimental, and possibly also therapeutic tools because they may have better selectivity than general inhibitors like carbenoxolone. Over the past ten years, several ...
The contractile system as a negative regulator of the connexin 43 hemichannel KU Leuven Universiteit Gent
The molecular mechanisms underlying the regulation of gap junction (GJ) channels based on the 43-kDa connexin isoform (Cx43) have been studied extensively. GJ channels are formed by the docking of opposed hemichannels in adjacent cells. Mounting data indicate that unopposed Cx43 hemichannels are also functional in the plasma membrane. However, our understanding of how Cx43-hemichannel opening and closing is regulated at the molecular level is ...
Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability KU Leuven Universiteit Gent
Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to ...
Connexin43 hemichannel targeting with TAT-Gap19 alleviates radiation-induced endothelial cell damage Universiteit Antwerpen KU Leuven Universiteit Gent
Background Emerging evidence indicates an excess risk of late occurring cardiovascular diseases, especially atherosclerosis, after thoracic cancer radiotherapy. Ionizing radiation (IR) induces cellular effects which may induce endothelial cell dysfunction, an early marker for atherosclerosis. In addition, intercellular communication through channels composed of transmembrane connexin proteins (Cxs), i.e. Gap junctions (direct cell-cell coupling) ...
Gap19, a Cx43 Hemichannel Inhibitor, Acts as a Gating Modifier That Decreases Main State Opening While Increasing Substate Gating KU Leuven Universiteit Gent
Cx43 hemichannels (HCs) are electrically and chemically gated transmembrane pores with low open probability and multiple conductance states, which makes kinetic studies of channel gating in large datasets challenging. Here, we developed open access software, named HemiGUI, to analyze HC gating transitions and investigated voltage-induced HC opening based on up to ≈4000 events recorded in HeLa-Cx43-overexpressing cells. We performed a detailed ...