The Journal of Neuroscience, August 1, 2000, 20(15):5639-5646
Facilitation of Recovery from Inactivation by External
Na+ and Location of the Activation Gate in Neuronal
Na+ Channels
Chung-Chin
Kuo1, 2 and
Shu-Yuan
Liao1
1 Department of Physiology, National Taiwan University
College of Medicine, and 2 Department of Neurology,
National Taiwan University Hospital, Taipei 100, Taiwan, Republic of
China.
Fast inactivation of the Na+ channel presumably
is produced by binding of the inactivating peptide (the "hinged
lid") to the internal pore mouth of the activated channel. It has
been shown that recovery from inactivation in Na+
channels begins with a delay, which corresponds to deactivation of the
channel, and is then followed by an exponential phase, which
corresponds to unbinding of the inactivating peptide. We found that the
exponential phase is ~1.6-fold faster in 150 mM than in 0 mM external Na+, but the initial delays
are the same. External Na+ also increases the late
steady-state Na+ current during a step
depolarization and shifts the inactivation curve accordingly but has no
effect on the activation and deactivation kinetics of the current.
Quantitative analysis of the data reveals that external
Na+ has the same facilitation effect on the
unbinding of the bound inactivating peptide whether the channel is
activated or deactivated but has no effect on the other gating
processes of the channel. These findings suggest that permeating
Na+ ions directly knock off the bound inactivating
peptide and that channel activation or deactivation does not affect the
accessibility of the bound inactivation peptide to external
Na+. The activation gate (the key gating change
transforming a Na+-nonconducting pore into a
Na+-conducting one) therefore should not be located
external to the inactivation gate, which presumably is already located
close to the internal end of the pore.
Key words:
Na+; Na+ channel; inactivation; deactivation; activation gate; inactivation gate
Copyright © 2000 Society for Neuroscience 0270-6474/00/20155639-08$05.00/0