%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 }