ArticleBiophysical journal1998
Extrapore residues of the S5-S6 loop of domain 2 of the voltage-gated skeletal muscle sodium channel (rSkM1) contribute to the mu-conotoxin GIIIA binding site.
Article in Biophysical journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Historical Perspective of the Characterization of Conotoxins Targeting Voltage-Gated Sodium Channels.Marine drugs · 2023Review
- Α- and β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO§-conotoxin GVIIJ.Journal of neurophysiology · 2015Article
- Article
- A disulfide tether stabilizes the block of sodium channels by the conotoxin μO§-GVIIJ.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.PloS one · 2014Article
- Biophysics, pathophysiology, and pharmacology of ion channel gating pores.Frontiers in pharmacology · 2014Review
- Mechanism and molecular basis for the sodium channel subtype specificity of µ-conopeptide CnIIIC.British journal of pharmacology · 2012Article
- A proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype.PloS one · 2012Article
- Article
- μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Mu-conotoxins as leads in the development of new analgesics.Molecules (Basel, Switzerland) · 2010Review
- Subtype-selective targeting of voltage-gated sodium channels.British journal of pharmacology · 2009Review
- The first gene-encoded amphibian neurotoxin.The Journal of biological chemistry · 2009Article
- Trans-channel interactions in batrachotoxin-modified rat skeletal muscle sodium channels: kinetic analysis of mutual inhibition between mu-conotoxin GIIIA derivatives and amine blockers.Biophysical journal · 2008Article
- Speeding the recovery from ultraslow inactivation of voltage-gated Na+ channels by metal ion binding to the selectivity filter: a foot-on-the-door?Biophysical journal · 2007Article
- Modeling P-loops domain of sodium channel: homology with potassium channels and interaction with ligands.Biophysical journal · 2005Article
- Conotoxins as sensors of local pH and electrostatic potential in the outer vestibule of the sodium channel.The Journal of general physiology · 2003Article
- Energetic localization of saxitoxin in its channel binding site.Biophysical journal · 2002Article
- Electrostatic and steric contributions to block of the skeletal muscle sodium channel by mu-conotoxin.The Journal of general physiology · 2002Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The tetradomain voltage-gated sodium channels from rat skeletal muscle (rSkM1) and from human heart (hH1) possess different sensitivities to the 22-amino-acid peptide toxin, mu-conotoxin GIIIA (mu-CTX). rSkM1 is sensitive (IC50 = 51.4 nM) whereas hH1 is relatively resistant (IC50 = 5700 nM) to the action of the toxin, a difference in sensitivity of >100-fold. The affinity of the mu-CTX for a chimera formed from domain 1 (D1), D2, and D3 from rSkM1and D4 from hH1 (SSSH; S indicates origin of domain is skeletal muscle and H indicates origin of domain is heart) was paradoxically increased approximately fourfold relative to that of rSkM1. The source of D3 is unimportant regarding the difference in the relative affinity of rSkM1 and hH1 for mu-CTX. Binding of mu-CTX to HSSS was substantially decreased (IC50 = 1145 nM). Another chimera with a major portion of D2 deriving form hH1 showed no detectable binding of mu-CTX (IC50 > 10 microM). These data indicate that D1 and, especially, D2 play crucial roles in forming the mu-CTX receptor. Charge-neutralizing mutations in D1 and D2 (Asp384, Asp762, and Glu765) had no effect on toxin binding. However, mutations at a neutral and an anionic site (residues 728 and 730) in S5-S6/D2 of rSkM1, which are not in the putative pore region, were found to decrease significantly the mu-CTX affinity with little effect on tetrodotoxin binding (</=1.3-fold increase in affinity). Furthermore, substitution at Asp730 with cysteine and exposure to Cd2+ or methanethiosulfonate reagents had no significant effect on sodium currents, consistent with this residue not contributing to the pore.
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