FN Archimer Export Format
PT J
TI A novel µ-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors
BT 
AF FAVREAU, Philippe
   BENOIT, Evelyne
   HOCKING, Henry G.
   CARLIER, Ludovic
   D'HOEDT, Dieter
   LEIPOLD, Enrico
   MARKGRAF, Rene
   SCHLUMBERGER, Sebastien
   CORDOVA, Marco A.
   GAERTNER, Hubert
   PAOLINI-BERTRAND, Marianne
   HARTLEY, Oliver
   TYTGAT, Jan
   HEINEMANN, Stefan H.
   BERTRAND, Daniel
   BOELENS, Rolf
   STOECKLIN, Reto
   MOLGO, Jordi
AS 1:1,2;2:2;3:3;4:3;5:4;6:5,6;7:5,6;8:2;9:7;10:1,8;11:8;12:8;13:9;14:5,6;15:4;16:3;17:1;18:2;
FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:;11:;12:;13:;14:;15:;16:;17:;18:;
C1 Atheris Labs, Bernex Geneva, Switzerland.
   CNRS, Lab Neurobiol & Dev, Inst Neurobiol Alfred Fessard, F-91198 Gif Sur Yvette, France.
   Bijvoet Ctr Biomol Res, Utrecht, Netherlands.
   Dept Neurosci, Geneva, Switzerland.
   Univ Jena, Dept Biophys, Ctr Mol Biomed, Jena, Germany.
   Jena Univ Hosp, Jena, Germany.
   Univ Chile, Fac Med, Inst Biomed Sci, Lab Marine Toxins,Program Physiol & Biophys, Santiago 7, Chile.
   Univ Geneva, Fac Med, Dept Struct Biol & Bioinformat, CH-1211 Geneva 4, Switzerland.
   Toxicol Lab, Louvain, Belgium.
C2 ATHERIS LABS, SWITZERLAND
   CNRS, FRANCE
   UNIV UTRECHT, NETHERLANDS
   UNIV GENEVA, SWITZERLAND
   UNIV JENA, GERMANY
   JENA UNIV HOSP, GERMANY
   UNIV CHILE, CHILE
   UNIV GENEVA, SWITZERLAND
   UNIV CATHOLIC LOUVAIN, BELGIUM
IF 5.07
TC 42
UR https://archimer.ifremer.fr/doc/00467/57830/60132.pdf
   https://archimer.ifremer.fr/doc/00467/57830/60133.pdf
   https://archimer.ifremer.fr/doc/00467/57830/60134.pdf
LA English
DT Article
CR TROPICAL DEEP-SEA BENTHOS
DE ;cone snail venom;mu-conotoxin;voltage-gated sodium channel;nicotinic acetylcholine receptor;myorelaxant;twitch tension;NMR structure
AB BACKGROUND AND PURPOSE The mu-conopeptide family is defined by its ability to block voltage-gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new mu-conopeptide (mu-CnIIIC) on a range of preparations and molecular targets to assess its potential as a myorelaxant. EXPERIMENTAL APPROACH mu-CnIIIC was sequenced, synthesized and characterized by its direct block of elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. mu-CnIIIC was also studied on HEK-293 cells expressing various rodent VGSCs and also on voltage-gated potassium channels and nicotinic acetylcholine receptors (nAChRs) to assess cross-interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data. KEY RESULTS Synthetic mu-CnIIIC decreased twitch tension in mouse hemidiaphragms (IC50= 150 nM), and displayed a higher blocking effect in mouse extensor digitorum longus muscles (IC = 46 nM), compared with mu-SIIIA, mu-SmIIIA and mu-PIIIA. mu-CnIIIC blocked NaV1.4 (IC50= 1.3 nM) and NaV1.2 channels in a long-lasting manner. Cardiac NaV1.5 and DRG-specific NaV1.8 channels were not blocked at 1 mu M. mu-CnIIIC also blocked the a3 beta 2 nAChR subtype (IC50= 450 nM) and, to a lesser extent, on the a7 and a4 beta 2 subtypes. Structure determination of mu-CnIIIC revealed some similarities to a-conotoxins acting on nAChRs. CONCLUSION AND IMPLICATIONS mu-CnIIIC potently blocked VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels. 
PY 2012
PD JUN
SO British Journal Of Pharmacology
SN 0007-1188
PU Wiley-blackwell
VL 166
IS 5
UT 000305560800015
BP 1654
EP 1668
DI 10.1111/j.1476-5381.2012.01837.x
ID 57830
ER

EF