Mechanisms of disease pathogenesis in long QT syndrome type 5.

ABSTRACT: KCNE1 associates with the pore-forming alpha-subunit KCNQ1 to generate the slow (I(Ks)) current in cardiac myocytes. Mutations in either KCNQ1 or KCNE1 can alter the biophysical properties of I(Ks) and mutations in KCNE1 underlie cases of long QT syndrome type 5 (LQT5). We previously investigated a mutation in KCNE1, T58P/L59P, which causes severe attenuation of I(Ks). However, how T58P/L59P acts to disrupt I(Ks) has not been determined. In this study, we investigate and compare the effects of T58P/L59P with three other LQT5 mutations (G52R, S74L, and R98W) on the biophysical properties of the current, trafficking of KCNQ1, and assembly of the I(Ks) channel. G52R and T58P/L59P produce currents that lack the kinetic behavior of I(Ks). In contrast, S74L and R98W both produce I(Ks)-like curre

SUBMITTER: Harmer SC 

PROVIDER: S-EPMC2822495 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature