Channelpedia

PubMed 14585842


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv11.1 , Kv3.4 , Kv7.1 , Slo1



Title: KvLQT1 modulates the distribution and biophysical properties of HERG. A novel alpha-subunit interaction between delayed rectifier currents.

Authors: Joachim R Ehrlich, Marc Pourrier, Manjula Weerapura, Nathalie Ethier, Aida M Marmabachi, Terence E Hebert, Stanley Nattel

Journal, date & volume: J. Biol. Chem., 2004 Jan 9 , 279, 1233-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14585842


Abstract
Cardiac repolarization is under joint control of the slow (IKs) and rapid (IKr) delayed rectifier currents. Experimental and clinical evidence indicates important functional interactions between these components. We hypothesized that there might be more direct interactions between the KvLQT1 and HERG alpha-subunits of IKs and IKr and tested this notion with a combination of biophysical and biochemical techniques. Co-expression of KvLQT1 with HERG in a mammalian expression system significantly accelerated HERG current deactivation at physiologically relevant potentials by increasing the contribution of the fast component (e.g. upon repolarization from +20 mV to -50 mV: from 20 +/- 3 to 32 +/- 5%, p < 0.05), making HERG current more like native IKr. In addition, HERG current density was approximately doubled (e.g. tail current after a step to +10 mV: 18 +/- 3 versus 39 +/- 7 pA/picofarad, p < 0.01) by co-expression with KvLQT1. KvLQT1 co-expression also increased the membrane immunolocalization of HERG by approximately 2-fold (p < 0.05). HERG and KvLQT1 co-immunolocalized in canine ventricular myocytes and co-immunoprecipitated in cultured Chinese hamster ovary cells as well as in native cardiac tissue, indicating physical interactions between HERG and KvLQT1 proteins in vitro and in vivo. Protein interaction assays also demonstrated binding of KvLQT1 (but not another K+ channel alpha-subunit, Kv3.4) to a C-terminal HERG glutathione S-transferase fusion protein. Co-expression with HERG did not affect the membrane localization or ionic current properties of KvLQT1. This study shows that the alpha-subunit of IKs can interact with and modify the localization and current-carrying properties of the alpha-subunit of IKr, providing potentially novel insights into the molecular function of the delayed rectifier current system.