Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.
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.
Li
Xiaoyan
X
Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214-3005, USA.
Bett
Glenna C L
GC
Jiang
Xuejun
X
Bondarenko
Vladimir E
VE
Morales
Michael J
MJ
Rasmusson
Randall L
RL
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
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