Kv1.4 encodes a slowly recovering transient outward current (I(to)),
which inactivates by a fast N-type (intracellular ball and chain)
mechanism but has slow recovery due to C-type inactivation. C-type
inactivation of the NH(2)-terminal deletion mutant (fKv1.4DeltaN)
was inhibited by 98 mM extracellular K$^+$ concentration (K$^+$(o)),
whereas N-type was unaffected. In 98 mM K$^+$(o), removal of
intracellular K$^+$ concentration (K$^+$(i)) speeded C-type
inactivation but had no effect on N-type inactivation, suggesting
that C-type inactivation is sensitive to K$^+$ binding to intracellular
sites. C-type inactivation is thought to involve closure of the extracellular
pore mouth. However, a valine to alanine mutation on the intracellular
side of S6 (V561A) of fKv1.4DeltaN alters recovery and results in
anomalous speeding of C-type inactivation with increasing K$^+$(o).
Extracellular pH (pH(o)) modulated both N- and C-type inactivation
through an S5-H5 linker histidine (H508) with acidosis speeding both
N- and C-type inactivation. Mutation of an extracellular lysine to
a tyrosine (K532Y) slowed C-type inactivation and inhibited the pH
dependence of both N- and C-type inactivation. These results suggest
that mutations, K$^+$, and pH modulate inactivation through
membrane-spanning mechanisms involving S6.
%0 Journal Article
%1 Li_2003_H71
%A Li, Xiaoyan
%A Bett, Glenna C L
%A Jiang, Xuejun
%A Bondarenko, Vladimir E
%A Morales, Michael J
%A Rasmusson, Randall L
%D 2003
%J Am. J. Physiol. Heart Circ. Physiol.
%K -U.S. 12388308 Acid Alanine, Algorithms, Amino Animals, Blockers, Calcium Calcium, Cardiac, Cardiovascular, Channel Channel, Channels, Computer Concentration, Conformation, Electrophysiology, Female, Ferrets, Gating, Gov't, Humans, Hydrogen, Hydrogen-Ion Ion Kinetics, Kv1.4 L-Type, Lysine, Models, Molecular Molecular, Mutation, Myocytes, Non, Non-P.H.S., Non-U.S. Oocytes, Osmotic P.H.S., Patch-Clamp Porosity, Potassium Potassium, Pressure, Research Sequence, Simulation, Substitution, Support, Techniques, Tyrosine, U.S. Valine, Voltage-Gated, Water, Xenopus Xenopus, laevis,
%N 1
%P H71--H80
%T Regulation of N- and C-type inactivation of Kv1.4 by pHo and K$^+$:
evidence for transmembrane communication.
%U http://ajpheart.physiology.org/cgi/content/full/284/1/H71
%V 284
%X Kv1.4 encodes a slowly recovering transient outward current (I(to)),
which inactivates by a fast N-type (intracellular ball and chain)
mechanism but has slow recovery due to C-type inactivation. C-type
inactivation of the NH(2)-terminal deletion mutant (fKv1.4DeltaN)
was inhibited by 98 mM extracellular K$^+$ concentration (K$^+$(o)),
whereas N-type was unaffected. In 98 mM K$^+$(o), removal of
intracellular K$^+$ concentration (K$^+$(i)) speeded C-type
inactivation but had no effect on N-type inactivation, suggesting
that C-type inactivation is sensitive to K$^+$ binding to intracellular
sites. C-type inactivation is thought to involve closure of the extracellular
pore mouth. However, a valine to alanine mutation on the intracellular
side of S6 (V561A) of fKv1.4DeltaN alters recovery and results in
anomalous speeding of C-type inactivation with increasing K$^+$(o).
Extracellular pH (pH(o)) modulated both N- and C-type inactivation
through an S5-H5 linker histidine (H508) with acidosis speeding both
N- and C-type inactivation. Mutation of an extracellular lysine to
a tyrosine (K532Y) slowed C-type inactivation and inhibited the pH
dependence of both N- and C-type inactivation. These results suggest
that mutations, K$^+$, and pH modulate inactivation through
membrane-spanning mechanisms involving S6.
@article{Li_2003_H71,
abstract = {Kv1.4 encodes a slowly recovering transient outward current (I(to)),
which inactivates by a fast N-type (intracellular ball and chain)
mechanism but has slow recovery due to C-type inactivation. C-type
inactivation of the NH(2)-terminal deletion mutant (fKv1.4DeltaN)
was inhibited by 98 mM extracellular {K}$^{+}$ concentration ([{K}$^{+}$](o)),
whereas N-type was unaffected. In 98 mM [{K}$^{+}$](o), removal of
intracellular {K}$^{+}$ concentration ([{K}$^{+}$](i)) speeded C-type
inactivation but had no effect on N-type inactivation, suggesting
that C-type inactivation is sensitive to {K}$^{+}$ binding to intracellular
sites. C-type inactivation is thought to involve closure of the extracellular
pore mouth. However, a valine to alanine mutation on the intracellular
side of S6 (V561A) of fKv1.4DeltaN alters recovery and results in
anomalous speeding of C-type inactivation with increasing [{K}$^{+}$](o).
Extracellular pH (pH(o)) modulated both N- and C-type inactivation
through an S5-H5 linker histidine (H508) with acidosis speeding both
N- and C-type inactivation. Mutation of an extracellular lysine to
a tyrosine (K532Y) slowed C-type inactivation and inhibited the pH
dependence of both N- and C-type inactivation. These results suggest
that mutations, [{K}$^{+}$], and pH modulate inactivation through
membrane-spanning mechanisms involving S6.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Li, Xiaoyan and Bett, Glenna C L and Jiang, Xuejun and Bondarenko, Vladimir E and Morales, Michael J and Rasmusson, Randall L},
biburl = {https://www.bibsonomy.org/bibtex/2b7da13a311d00e1f94f0efdeea9ea544/hake},
description = {The whole bibliography file I use.},
file = {Li_2003_H71.pdf:Li_2003_H71.pdf:PDF},
interhash = {2d171062d304a4e5a4074341eff0db68},
intrahash = {b7da13a311d00e1f94f0efdeea9ea544},
journal = {Am. J. Physiol. Heart Circ. Physiol.},
keywords = {-U.S. 12388308 Acid Alanine, Algorithms, Amino Animals, Blockers, Calcium Calcium, Cardiac, Cardiovascular, Channel Channel, Channels, Computer Concentration, Conformation, Electrophysiology, Female, Ferrets, Gating, Gov't, Humans, Hydrogen, Hydrogen-Ion Ion Kinetics, Kv1.4 L-Type, Lysine, Models, Molecular Molecular, Mutation, Myocytes, Non, Non-P.H.S., Non-U.S. Oocytes, Osmotic P.H.S., Patch-Clamp Porosity, Potassium Potassium, Pressure, Research Sequence, Simulation, Substitution, Support, Techniques, Tyrosine, U.S. Valine, Voltage-Gated, Water, Xenopus Xenopus, laevis,},
month = Jan,
number = 1,
pages = {H71--H80},
pdf = {Li_2003_H71.pdf},
pii = {00392.2002},
pmid = {12388308},
timestamp = {2009-06-03T11:21:20.000+0200},
title = {Regulation of N- and C-type inactivation of Kv1.4 by pHo and {K}$^{+}$:
evidence for transmembrane communication.},
url = {http://ajpheart.physiology.org/cgi/content/full/284/1/H71},
volume = 284,
year = 2003
}