Channelpedia

PubMed 11160624


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.2 , Kv1.4



Title: Differential sensitivity of Kv1.4, Kv1.2, and their tandem channel to acidic pH: involvement of a histidine residue in high sensitivity to acidic pH.

Authors: K Ishii, K Nunoki, T Yamagishi, H Okada, N Taira

Journal, date & volume: J. Pharmacol. Exp. Ther., 2001 Feb , 296, 405-11

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11160624


Abstract
We studied the effects of acidic pH on the currents through voltage-gated K+ channels, Kv1.2, Kv1.4, and their tandem construct (Kv1.4-Kv1.2). Kv1.4 currents were inhibited considerably under acidic pH in a voltage-independent manner, whereas Kv1.2 currents were less inhibited in an apparently voltage-dependent manner. The apparent voltage-dependent block of Kv1.2 currents was mostly ascribed to the shift of activation voltage, which is probably due to surface charge effects of H+ ions. Mutagenesis analysis identified the histidine residue at 508 (H508) in the S5-H5 linker as a molecular determinant of pH sensitivity of Kv1.4. Currents through the tandem channel showed intermediate characteristics between the two parent channels in both sensitivity and voltage dependence of pH effects. Our results suggest that 1) the H508 plays a critical role in determining pH sensitivity of Kv1.4; and 2) the two parent channels, Kv1.2 and Kv1.4, are involved in determining pH sensitivity and apparent voltage dependence of the tandem channel.