Referenced in: none

Automatically associated channels: Kir2.3

Title: Generation of functional ion-channel tools by E3 targeting.

Authors: Shang-Zhong Xu, Fanning Zeng, Ming Lei, Jing Li, Bin Gao, Chenliang Xiong, Asipu Sivaprasadarao, David J Beech

Journal, date & volume: Nat. Biotechnol., 2005 Oct , 23, 1289-93

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16170312

Abstract
Here we describe a strategy for generating ion-channel inhibitors. It takes advantage of antibody specificity combined with a pattern recognition approach that targets the third extracellular region (E3) of a channel. To test the concept, we first focused on TRPC5, a member of the transient receptor potential (TRP) calcium channel family, the study of which has been hindered by poor pharmacological tools. Extracellular application of E3-targeted anti-TRPC5 antibody led to a specific TRPC5 inhibitor, enabling TRPC5 to be distinguished from its closest family members, and TRPC5 function to be explored in a relatively intractable physiological system. E3 targeting was further applied to voltage-gated sodium channels, leading to discovery of a subtype-specific inhibitor of Na(V)1.5. These examples illustrate the potential power of E3 targeting as a systematic method for producing gene-type specific ion-channel inhibitors for use in routine assays on cells or tissues from a range of species and having therapeutic potential.