On site of action of grayanotoxin in domain 4 segment 6 of rat skeletal muscle sodium channel
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概要
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Grayanotoxin I (GTX I) is a diterpenoid extracted from the family of Ericaceae that binds to Na+ channels and causes persistent activation. We investigated the interaction of GTX I with the amino acid residues I1575, F1579 and Y1586 in transmembrane segment D4S6 of μ1. In F1579A, GTX shifted the threshold potential about 50 mV in the hyperpolarizing direction and modified Na+ channels twice as efficiently as that in WT. In contrast, these GTX effects were eliminated completely in the I1575A mutant and were reduced substantially in mutant Y1586A. Lysine substitution for F1579 significantly reduced and for Y1586 completely eradicated the GTX-effect. Our data suggest that the GTX receptor site shares overlapping but not-identical molecular determinants with BTX in D4S6 as well as having common molecular determinants in D1S6.
- 2000-01-07
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