ArticleThe Journal of general physiology2008
Divalent cations regulate connexin hemichannels by modulating intrinsic voltage-dependent gating.
Article in The Journal of general physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.Nature communications · 2026Article
- Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.bioRxiv : the preprint server for biology · 2025Article
- Model-based evaluation of connexin hemichannel permeability.Computational and structural biotechnology journal · 2025Article
- A pore locus in the E1 domain differentially regulates Cx26 and Cx30 hemichannel function.The Journal of general physiology · 2024Article
- Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26.International journal of molecular sciences · 2024Article
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures.Biology · 2024Review
- Unnexin is a protein subunit of a large-pore channel expressed by unicellular organisms.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The circadian regulation of extracellular ATP.Purinergic signalling · 2023Review
- Pathological mechanisms of connexin26-related hearing loss: Potassium recycling, ATP-calcium signaling, or energy supply?Frontiers in molecular neuroscience · 2022Review
- Beyond the Channels: Adhesion Functions of Aquaporin 0 and Connexin 50 in Lens Development.Frontiers in cell and developmental biology · 2022Review
- Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens.Frontiers in physiology · 2022Review
- Lens Connexin Channels Show Differential Permeability to Signaling Molecules.International journal of molecular sciences · 2020Review
- Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel.Science advances · 2020Article
- Role of ROS/RNS in Preeclampsia: Are Connexins the Missing Piece?International journal of molecular sciences · 2020Review
- Inner Ear Connexin Channels: Roles in Development and Maintenance of Cochlear Function.Cold Spring Harbor perspectives in medicine · 2019Review
- Contribution of Connexin Hemichannels to the Decreases in Cell Viability Induced by Linoleic Acid in the Human Lens Epithelial Cells (HLE-B3).Frontiers in physiology · 2019Article
- Electrical coupling and its channels.The Journal of general physiology · 2018Review
- Cx26 partial loss causes accelerated presbycusis by redox imbalance and dysregulation of Nfr2 pathway.Redox biology · 2018Article
- The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels.The Journal of general physiology · 2018Article
5 more citing papers are in PubMed but not listed here.
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2 authors.
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Abstract
Connexin hemichannels are robustly regulated by voltage and divalent cations. The basis of voltage-dependent gating, however, has been questioned with reports that it is not intrinsic to hemichannels, but rather is derived from divalent cations acting as gating particles that block the pore in a voltage-dependent manner. Previously, we showed that connexin hemichannels possess two types of voltage-dependent gating, termed V(j) and loop gating, that in Cx46 operate at opposite voltage polarities, positive and negative, respectively. Using recordings of single Cx46 hemichannels, we found both forms of gating persist in solutions containing no added Mg(2+) and EGTA to chelate Ca(2+). Although loop gating persists, it is significantly modulated by changing levels of extracellular divalent cations. When extracellular divalent cation concentrations are low, large hyperpolarizing voltages, exceeding -100 mV, could still drive Cx46 hemichannels toward closure. However, gating is characterized by continuous flickering of the unitary current interrupted by occasional, brief sojourns to a quiet closed state. Addition of extracellular divalent cations, in this case Mg(2+), results in long-lived residence in a quiet closed state, suggesting that hyperpolarization drives the hemichannel to close, perhaps by initiating movements in the extracellular loops, and that divalent cations stabilize the fully closed conformation. Using excised patches, we found that divalent cations are only effective from the extracellular side, indicative that the binding site is not cytoplasmic or in the pore, but rather extracellular. V(j) gating remains essentially unaffected by changing levels of extracellular divalent cations. Thus, we demonstrate that both forms of voltage dependence are intrinsic gating mechanisms in Cx46 hemichannels and that the action of external divalent cations is to selectively modulate loop gating.
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