Inactivation is the process by which an open channel enters a stable
nonconducting conformation after a depolarizing change in membrane
potential. Inactivation is a widespread property of many different
types of voltage-gated ion channels. Recent advances in the molecular
biology of K$^+$ channels have elucidated two mechanistically
distinct types of inactivation, N-type and C-type. N-type inactivation
involves occlusion of the intracellular mouth of the pore through
binding of a short segment of residues at the extreme N-terminal.
In contrast to this "tethered ball" mechanism of N-type inactivation,
C-type inactivation involves movement of conserved core domain residues
that result in closure of the external mouth of the pore. Although
C-type inactivation can show rapid kinetics that approach those observed
for N-type inactivation, it is often thought of as a slowly developing
and slowly recovering process. Current models of C-type inactivation
also suggest that this process involves a relatively localized change
in conformation of residues near the external mouth of the permeation
pathway. The rate of C-type inactivation and recovery can be strongly
influenced by other factors, such as N-type inactivation, drug binding,
and changes in K$^+$o. These interactions make C-type inactivation
an important biophysical process in determining such physiologically
important properties as refractoriness and drug binding. C-type inactivation
is currently viewed as arising from small-scale rearrangements at
the external mouth of the pore. This review will examine the multiplicity
of interactions of C-type inactivation with N-terminal-mediated inactivation
and drug binding that suggest that our current view of C-type inactivation
is incomplete. This review will suggest that C-type inactivation
must involve larger-scale movements of transmembrane-spanning domains
and that such movements contribute to the diversity of kinetic properties
observed for C-type inactivation.
%0 Journal Article
%1 Rasm_1998_739
%A Rasmusson, R. L.
%A Morales, M. J.
%A Wang, S.
%A Liu, S.
%A Campbell, D. L.
%A Brahmajothi, M. V.
%A Strauss, H. C.
%D 1998
%J Circ. Res.
%K 9562433 Allosteric Animals, Binding, Channel Channels, Fr, Gating, Heart, Humans, Ion Membrane Peptide Potassium Potentials, Protein Regulation, agments,
%N 7
%P 739--750
%T Inactivation of voltage-gated cardiac K$^+$ channels.
%V 82
%X Inactivation is the process by which an open channel enters a stable
nonconducting conformation after a depolarizing change in membrane
potential. Inactivation is a widespread property of many different
types of voltage-gated ion channels. Recent advances in the molecular
biology of K$^+$ channels have elucidated two mechanistically
distinct types of inactivation, N-type and C-type. N-type inactivation
involves occlusion of the intracellular mouth of the pore through
binding of a short segment of residues at the extreme N-terminal.
In contrast to this "tethered ball" mechanism of N-type inactivation,
C-type inactivation involves movement of conserved core domain residues
that result in closure of the external mouth of the pore. Although
C-type inactivation can show rapid kinetics that approach those observed
for N-type inactivation, it is often thought of as a slowly developing
and slowly recovering process. Current models of C-type inactivation
also suggest that this process involves a relatively localized change
in conformation of residues near the external mouth of the permeation
pathway. The rate of C-type inactivation and recovery can be strongly
influenced by other factors, such as N-type inactivation, drug binding,
and changes in K$^+$o. These interactions make C-type inactivation
an important biophysical process in determining such physiologically
important properties as refractoriness and drug binding. C-type inactivation
is currently viewed as arising from small-scale rearrangements at
the external mouth of the pore. This review will examine the multiplicity
of interactions of C-type inactivation with N-terminal-mediated inactivation
and drug binding that suggest that our current view of C-type inactivation
is incomplete. This review will suggest that C-type inactivation
must involve larger-scale movements of transmembrane-spanning domains
and that such movements contribute to the diversity of kinetic properties
observed for C-type inactivation.
@article{Rasm_1998_739,
abstract = {Inactivation is the process by which an open channel enters a stable
nonconducting conformation after a depolarizing change in membrane
potential. Inactivation is a widespread property of many different
types of voltage-gated ion channels. Recent advances in the molecular
biology of {K}$^{+}$ channels have elucidated two mechanistically
distinct types of inactivation, N-type and C-type. N-type inactivation
involves occlusion of the intracellular mouth of the pore through
binding of a short segment of residues at the extreme N-terminal.
In contrast to this "tethered ball" mechanism of N-type inactivation,
C-type inactivation involves movement of conserved core domain residues
that result in closure of the external mouth of the pore. Although
C-type inactivation can show rapid kinetics that approach those observed
for N-type inactivation, it is often thought of as a slowly developing
and slowly recovering process. Current models of C-type inactivation
also suggest that this process involves a relatively localized change
in conformation of residues near the external mouth of the permeation
pathway. The rate of C-type inactivation and recovery can be strongly
influenced by other factors, such as N-type inactivation, drug binding,
and changes in [{K}$^{+}$]o. These interactions make C-type inactivation
an important biophysical process in determining such physiologically
important properties as refractoriness and drug binding. C-type inactivation
is currently viewed as arising from small-scale rearrangements at
the external mouth of the pore. This review will examine the multiplicity
of interactions of C-type inactivation with N-terminal-mediated inactivation
and drug binding that suggest that our current view of C-type inactivation
is incomplete. This review will suggest that C-type inactivation
must involve larger-scale movements of transmembrane-spanning domains
and that such movements contribute to the diversity of kinetic properties
observed for C-type inactivation.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Rasmusson, R. L. and Morales, M. J. and Wang, S. and Liu, S. and Campbell, D. L. and Brahmajothi, M. V. and Strauss, H. C.},
biburl = {https://www.bibsonomy.org/bibtex/21ca04de37703d942b2638136df4eb00e/hake},
description = {The whole bibliography file I use.},
file = {Rasm_1998_739.pdf:Rasm_1998_739.pdf:PDF},
interhash = {cae9aa5e25ef8d0fa4871c596264bfd6},
intrahash = {1ca04de37703d942b2638136df4eb00e},
journal = {Circ. Res.},
keywords = {9562433 Allosteric Animals, Binding, Channel Channels, Fr, Gating, Heart, Humans, Ion Membrane Peptide Potassium Potentials, Protein Regulation, agments,},
month = Apr,
number = 7,
pages = {739--750},
pmid = {9562433},
timestamp = {2009-06-03T11:21:26.000+0200},
title = {Inactivation of voltage-gated cardiac {K}$^{+}$ channels.},
volume = 82,
year = 1998
}