ArticleBiophysical journal2012
Aspartic acid residue D3 critically determines Cx50 gap junction channel transjunctional voltage-dependent gating and unitary conductance.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Calcium induced N-terminal gating and pore collapse in connexin-46/50 gap junctions.bioRxiv : the preprint server for biology · 2025Article
- Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures.Biology · 2024Review
- The Hydrophobic Residues in Amino Terminal Domains of Cx46 and Cx50 Are Important for Their Gap Junction Channel Ion Permeation and Gating.International journal of molecular sciences · 2022Article
- Connexin 46 and connexin 50 gap junction channel properties are shaped by structural and dynamic features of their N-terminal domains.The Journal of physiology · 2021Article
- Structural determinants underlying permeant discrimination of the Cx43 hemichannel.The Journal of biological chemistry · 2019Article
- Article
- Gap junction structure: unraveled, but not fully revealed.F1000Research · 2017Review
- Specificity of the connexin W3/4 locus for functional gap junction formation.Channels (Austin, Tex.) · 2016Article
- Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels.Frontiers in physiology · 2013Review
- Properties of two cataract-associated mutations located in the NH2 terminus of connexin 46.American journal of physiology. Cell physiology · 2013Article
- Heterotypic connexin50/connexin50 mutant gap junction channels reveal interactions between two hemichannels during transjunctional voltage-dependent gating.The Journal of physiology · 2012Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous studies have suggested that the aspartic acid residue (D) at the third position is critical in determining the voltage polarity of fast V(j)-gating of Cx50 channels. To test whether another negatively charged residue (a glutamic acid residue, E) could fulfill the role of the D3 residue, we generated the mutant Cx50D3E. V(j)-dependent gating properties of this mutant channel were characterized by double-patch-clamp recordings in N2A cells. Macroscopically, the D3E substitution reduced the residual conductance (G(min)) to near zero and outwardly shifted the half-inactivation voltage (V(0)), which is a result of both a reduced aggregate gating charge (z) and a reduced free-energy difference between the open and closed states. Single Cx50D3E gap junction channels showed reduced unitary conductance (γ(j)) of the main open state, reduced open dwell time at ±40 mV, and absence of a long-lived substate. In contrast, a G8E substitution tested to compare the effects of the E residue at the third and eighth positions did not modify the V(j)-dependent gating profile or γ(j). In summary, this study is the first that we know of to suggest that the D3 residue plays an essential role, in addition to serving as a negative-charge provider, as a critical determinant of the V(j)-dependent gating sensitivity, open-closed stability, and unitary conductance of Cx50 gap junction channels.
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