Referenced in: none

Automatically associated channels: SK1 , SK2 , SK3

Title: Subtype-specific, bi-component inhibition of SK channels by low internal pH.

Authors: Torben Peitersen, Charlotte Hougaard, Thomas Jespersen, Nanna K Jorgensen, Søren-Peter Olesen, Morten Grunnet

Journal, date & volume: Biochem. Biophys. Res. Commun., 2006 May 12 , 343, 943-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16566895

Abstract
The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+-activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6.4 in the order of sensitivity: SK1>SK3>SK2. The inhibition increased with the transmembrane voltage. In saturating internal Ca2+, the inhibition was abolished for SK1-3 channels at negative potentials, indicating a [Ca2+]i-dependent mode of inhibition. Application of 50 microM 1-ethyl-2-benzimidazolone was able to potentiate SK3 current to the same extent as at neutral pH(i). We conclude that SK1-3 all are inhibited by low pH(i). We suggest two components of inhibition: a [Ca2+]i-dependent component, likely involving the SK beta-subunits calmodulin, and a voltage-dependent component, consistent with a pore-blocking effect. This pH(i)-dependent inhibition can be reversed pharmacologically.