title: Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.
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.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214-3005, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Glenna C L
authors.initials: GC
authors.lastname: Bett
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Bondarenko
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morales
authors.forename: Randall L
authors.initials: RL
authors.lastname: Rasmusson
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D005260:Female; D006859:Hydrogen / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D051665:Kv1.4 Potassium Channel; D008239:Lysine; D009154:Mutation / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D014443:Tyrosine; D014633:Valine; D014982:Xenopus laevis
chemical_list: D051665:Kv1.4 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D014443:Tyrosine; D006859:Hydrogen; D014633:Valine; D008239:Lysine; D000409:Alanine; D011188:Potassium