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- W2006258673 abstract "The cationic dye methylene blue (MB+) blocks INa in a voltage and time-dependent manner and exhibits no frequency dependent block at 1 Hz when internally perfused in normal or pronase-treated crayfish axons. Peak INa decreases with increasing MB+ concentrations in the range 50 microM to 5 mM, but the blocking time constant approaches an asymptote at concentrations above 500 microM. IgON is not noticeably affected by internal MB+ at concentrations of 500 microM or below, in the absence of external tetrodotoxin (TTX). However, 5 mM MB+ produces a visible suppression of IgON that is reversible following washout. A pseudo-first-order analysis of MB+ blocking kinetics suggests a drug binding site deep in the transmembrane voltage field (dz = 0.85, KD = 11 microM at 0 mV). The voltage sensitivity of the individual rate constants is highly asymmetric, suggesting that the major energy barrier for MB+ is very close to the axoplasmic margin of the voltage field. Reversing the Na+ gradient and direction of INa has little effect on the kinetics of MB+ block. The kinetic properties of state-dependent vs. state-independent blocking schemes are investigated and compared with our observations of MB+ block. Analysis of hooked sodium tail currents following depolarization to various test potentials demonstrates quantitatively that MB+ binds in a state-dependent manner to open sodium channels. The appropriateness of first-order kinetic analysis of drug block is then considered in light of these observations." @default.
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- W2006258673 title "Kinetic analysis of sodium channel block by internal methylene blue in pronased crayfish giant axons" @default.
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- W2006258673 doi "https://doi.org/10.1016/s0006-3495(84)84014-x" @default.
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