Volume 17, Number 10,
Issue of May 15, 1997
pp. 3436-3444
Copyright ©1997 Society for Neuroscience
Deactivation Retards Recovery from Inactivation in Shaker
K+ Channels
Received Jan. 3, 1997; revised Feb. 24, 1997; accepted Feb. 27, 1997.
Chung-Chin Kuo
Department of Physiology, National Taiwan University College of
Medicine, and Department of Neurology, National Taiwan University
Hospital, Taipei 100, Taiwan, Republic of China
In Na+ channels, recovery from inactivation
begins with a delay, followed by an exponential course, and
hyperpolarization shortens the delay as well as hastens the entire
exponential phase. These findings have been taken to indicate that
Na+ channels must deactivate to recover from inactivation,
and deactivation facilitates the unbinding of the inactivating
particle. In contrast, it is demonstrated in this study that recovery
from inactivation in Shaker K+ channels begins with no
delay on repolarization. Moreover, hyperpolarization hastens only the
initial phase (fast component) of recovery yet retards the later phases
of recovery by increasing the proportion of slow components. The time
course of slow inward "tail" K+ currents, which
presumably result from the open state(s) traversed by the recovering
inactivated channel, always matches the fast, but not the slow,
components of recovery, suggesting that the fast and the slow
components primarily correspond to recovery via the open state
(unblocking of the inactivating particle before channel deactivation)
and via the closed state (deactivation before unblocking),
respectively. Besides, changing external K+ concentration
effectively alters the absolute value of the initial recovery speed,
but not its voltage dependence. It seems that Shaker K+
channel deactivation hinders, rather than facilitates, the unbinding of
the inactivating particle and therefore retards recovery from inactivation, whereas external K+ may enhance unbinding of
the inactivating particle by binding to a site located near the
external entrance of the pore.
Key words:
two-electrode voltage clamp;
Shaker K+
channel;
deactivation;
ball and chain model of inactivation;
recovery
from inactivation;
K+ ion binding site