Ca2+-Calmodulin and PIP2 interactions at the proximal C-terminus of Kv7 channels. Issue 6 (2nd November 2017)

• Record Type: Journal Article
• Authors: Tobelaim, William S.; Dvir, Meidan; Lebel, Guy; Cui, Meng; Buki, Tal; Peretz, Asher; Marom, Milit; Haitin, Yoni; Logothetis, Diomedes E.; Hirsch, Joel A.; Attali, Bernard
• Is Part Of: Channels. Volume 11:Issue 6(2017)
• Page Start: 686
• Page End: 695
• Publication Date: 2017-11-02
• Subjects: calmodulin -- Kv7 -- KCNQ -- Potassium channel -- PIP2; Ion channels -- Periodicals; 572.3
• DOI: 10.1080/19336950.2017.1388478
• Languages: English
• ISSNs: 1933-6950

Abstract

ABSTRACT: In the heart, co-assembly of Kv7.1 with KCNE1 produces the slow IKS potassium current, which repolarizes the cardiac action potential and mutations in human Kv7.1 and KCNE1 genes cause cardiac arrhythmias. The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4, 5-bisphosphate (PIP2 ) and recently we revealed the competition of PIP2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation. Data indicated that PIP2 and Ca 2+ -CaM perform the same function on IKS channel gating to stabilize the channel open state. Here we show that similar features were observed for Kv7.1 currents expressed alone. We also find that conservation of homologous residues in helix B of other Kv7 subtypes confer similar competition of Ca 2+ -CaM with PIP2 binding to their proximal C-termini and suggest that PIP2-CaM interactions converge to Kv7 helix B to modulates channel activity in a Kv7 subtype-dependent manner.