The Journal of General Physiology, Vol 80, 641-662, Copyright © 1982 by The Rockefeller University Press
Simulation of Na channel inactivation by thiazine dyes
CM Armstrong and RS Croop
Some dyes of the methylene blue family serve as artificial inactivators of
the sodium channels when present inside squid axons at a concentration of
approximately 0.1 mM. The dyes restore a semblance of inactivation after
normal inactivation has been destroyed by pronase. In fibers that
inactivate normally, the dyes hasten the decay of sodium current. Many
dye-blocked channels conduct transiently on exit of the dye molecule after
repolarization to the holding potential. In contrast, normally inactivated
channels do not conduct during recovery from inactivation. Kinetic evidence
shows that inactivation of a dye- blocked channel is unlikely or
impossible, which suggests that dye molecules compete with inactivation
"particles" for the same site. In the absence of tetrodotoxin, the dyes do
not affect the ON gating current unless the interpulse interval is very
short. If sufficient equilibration time is allowed during a pulse, the
initial amplitude of the OFF gating current is reduced to near zero. This
suggests that a dye molecule is a Na channel completely blocks that
channel's gating current, even the fraction that is resistant to normal
inactivation. Dyes block INa and Ig with the same time course. This
provides the strongest evidence to date that virtually all of recorded
"gating current" is associated with Na channels. Tetrodotoxin greatly slows
dissociation of dye molecules from Na channels and reduced gating current
during both opening and closing of the channels.
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