PubMed 23272793

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv7.1

Title: KCNE genetics and pharmacogenomics in cardiac arrhythmias: much ado about nothing?

Authors: Geoffrey W Abbott

Journal, date & volume: Expert Rev Clin Pharmacol, 2013 Jan , 6, 49-60

PubMed link:

Voltage-gated ion channels respond to changes in membrane potential with conformational shifts that either facilitate or stem the movement of charged ions across the cell membrane. This controlled movement of ions is particularly important for the action potentials of excitable cells such as cardiac myocytes and therefore essential for timely beating of the heart. Inherited mutations in ion channel genes and in the genes encoding proteins that regulate them can cause lethal cardiac arrhythmias either by direct channel disruption or by altering interactions with therapeutic drugs, the best-understood example of both these scenarios being long QT syndrome (LQTS). Unsurprisingly, mutations in the genes encoding ion channel pore-forming α subunits underlie the large majority (~90%) of identified cases of inherited LQTS. Given that inherited LQTS is comparatively rare in itself (~0.04% of the US population), is pursuing study of the remaining known and unknown LQTS-associated genes subject to the law of diminishing returns? Here, with a particular focus on the KCNE family of single transmembrane domain K(+) channel ancillary subunits, the significance to cardiac pharmacogenetics of ion channel regulatory subunits is discussed.