Referenced in: none

Automatically associated channels: Kv1.4 , Slo1

Title: Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.

Authors: Xiaoyan Li, Glenna C L Bett, Xuejun Jiang, Vladimir E Bondarenko, Michael J Morales, Randall L Rasmusson

Journal, date & volume: Am. J. Physiol. Heart Circ. Physiol., 2003 Jan , 284, H71-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12388308

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.