RT Journal Article
SR Electronic
T1 A Uniquely Selective Inhibitor of the Mammalian Fetal Neuromuscular Nicotinic Acetylcholine Receptor
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 732
OP 736
DO 10.1523/JNEUROSCI.4065-04.2005
VO 25
IS 3
A1 Teichert, Russell W.
A1 Rivier, Jean
A1 Torres, Josep
A1 Dykert, John
A1 Miller, Charleen
A1 Olivera, Baldomero M.
YR 2005
UL http://www.jneurosci.org/content/25/3/732.abstract
AB We have purified and characterized a novel conotoxin from the venom of Conus obscurus, which has the unique property of selectively and potently inhibiting the fetal form of the mammalian neuromuscular nicotinic acetylcholine receptor (nAChR) (α1β1γδ-subunits). Although this conotoxin, αA-conotoxin OIVB (αA-OIVB), is a high-affinity antagonist (IC50 of 56 nm) of the fetal muscle nAChR, it has >1800-fold lower affinity for the adult muscle nAChR (α1β1ϵδ-subunits) and virtually no inhibitory activity at a high concentration on various neuronal nAChRs (IC50 > 100 μm in all cases). The peptide (amino acid sequence, CCGVONAACPOCVCNKTCG), with three disulfide bonds, has been chemically synthesized in a biologically active form. Although the neuromuscular nAChRs are perhaps the most extensively characterized of the receptors/ion channels of the nervous system, the precise physiological roles of the fetal form of the muscle nAChR are essentially unknown.αA-OIVB is a potentially important tool for delineating the functional roles ofα1β1γδ receptors in normal development, as well as in various adult tissues and in pathological states. In addition to its potential as a research tool, αA-OIVB may have some direct biomedical applications. Figure 1. Purification of αA-OIVB. A, Milked venom was fractionated on a reversed-phase C8 HPLC column. B, Further purification of the fraction marked by an arrow in A providedαA-OIVB as the major peak, also marked by an arrow in B.Figure 2. Comigration of synthetic and native αA-OIVB using CZE (100 mm Na2HPO4 buffer at pH 2.5 and a voltage of 15 kV). AUFS, Absorbance units full scale.