ArticleThe Journal of physiology2004
Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 78 citations in OpenAlex.
- Hydrogen peroxide reduces Cx40, Cx43, and Cx45 gap junction function.Cell and tissue research · 2026Article
- Article
- The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium.Biomolecules · 2022Article
- 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
- Interrogation of Carboxy-Terminus LocalizedInternational 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
- Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS.Biochemistry (Moscow) Supplement. Series A, Membrane and cell biology · 2021Article
- Molecular basis of junctional current rectification at an electrical synapse.Science advances · 2020Article
- Structural determinants underlying permeant discrimination of the Cx43 hemichannel.The Journal of biological chemistry · 2019Article
- Structure and Function of Cochlear Gap Junctions and Implications for the Translation of Cochlear Gene Therapies.Frontiers in cellular neuroscience · 2019Article
- Two Forms of Electrical Transmission Between Neurons.Frontiers in molecular neuroscience · 2018Article
- Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.Frontiers in physiology · 2018Article
- Inhibitors of connexin and pannexin channels as potential therapeutics.Pharmacology & therapeutics · 2017Review
- The electrical synapse: Molecular complexities at the gap and beyond.Developmental neurobiology · 2017Review
- Gap junction structure: unraveled, but not fully revealed.F1000Research · 2017Review
- Gap Junction in the Teleost Fish Lineage: Duplicated Connexins May Contribute to Skin Pattern Formation and Body Shape Determination.Frontiers in cell and developmental biology · 2017Review
- Specificity of the connexin W3/4 locus for functional gap junction formation.Channels (Austin, Tex.) · 2016Article
- Spermidine, but not spermine, is essential for pigment pattern formation in zebrafish.Biology open · 2016Article
- The Physiological Characterization of Connexin41.8 and Connexin39.4, Which Are Involved in the Striped Pattern Formation of Zebrafish.The Journal of biological chemistry · 2016Article
- Determinants of Cx43 Channel Gating and Permeation: The Amino Terminus.Biophysical journal · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Connexin40 (Cx40) contains a specific binding site for spermine (affinity approximately 100 microm) whereas connexin43 (Cx43) is unaffected by identical concentrations of intracellular spermine. Replacement of two unique glutamate residues, E9 and E13, from the cytoplasmic amino terminal domain of Cx40 with the corresponding lysine residues from Cx43 eliminated the block by 2 mm spermine, reduced the transjunctional voltage (V(j)) gating sensitivity, and reduced the unitary conductance of this Cx40E9,13K gap junction channel protein. The single point mutations, Cx40E9K and Cx40E13K, predominantly affected the residual conductance state (G(min)) and V(j) gating properties, respectively. Heterotypic pairing of Cx40E9,13K with wild-type Cx40 in murine neuro2A (N2A) cells produced a strongly rectifying gap junction reminiscent of the inward rectification properties of the Kir (e.g. Kir2.x) family of potassium channels. The reciprocal Cx43K9,13E mutant protein exhibited reduced V(j) sensitivity, but displayed much less rectification in heterotypic pairings with wtCx43, negligible changes in the unitary channel conductance, and remained insensitive to spermine block. These data indicate that the connexin40 amino terminus may form a critical cytoplasmic pore-forming domain that serves as the receptor for V(j)-dependent closure and block by intracellular polyamines. Functional reciprocity between Cx40 and Cx43 gap junctions involves other amino acid residues in addition to the E or K 9 and 13 loci located on the amino terminal domain of these two connexins.
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