Abstract

Ion channels are transmembrane proteins that selectively allow ions to flow across the plasma membrane and play key roles in diverse biological processes. A multitude of diseases, called channelopathies, such as epilepsies, muscle paralysis, pain syndromes, cardiac arrhythmias or hypoglycemia are due to ion channel mutations. A wide corpus of literature is available on ion channels, covering both their functions and their roles in disease. The research community needs to access this data in a user-friendly, yet systematic manner. However, extraction and integration of this increasing amount of data have been proven to be difficult because of the lack of a standardized vocabulary that describes the properties of ion channels at the molecular level. To address this, we have developed Ion Channel ElectroPhysiology Ontology (ICEPO), an ontology that allows one to annotate the electrophysiological parameters of the voltage-gated class of ion channels. This ontology is based on a three-state model of ion channel gating describing the three conformations/states that an ion channel can adopt: closed, open and inactivated. This ontology supports the capture of voltage-gated ion channel electrophysiological data from the literature in a structured manner and thus enables other applications such as querying and reasoning tools. Here, we present ICEPO (ICEPO ftp site: ftp://ftp.nextprot.org/pub/current_release/controlled_vocabularies/), as well as examples of its use.

Highlights

  • Ion channels are pore-forming transmembrane proteins that selectively allow ions to flow across the plasma membrane according to electro-chemical gradients

  • This study presents the first development of Ion Channel ElectroPhysiology Ontology (ICEPO), an ontology that describes selected molecular steps of voltagegated ion channel function

  • With minor modifications and extensions, the ontology could be used to annotate the electrophysiological parameters of any class of ion channel

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Summary

Introduction

Ion channels are pore-forming transmembrane proteins that selectively allow ions to flow across the plasma membrane according to electro-chemical gradients. Ion channels that open following a change in the membrane voltage potential are known as ‘voltage-gated ion channels’ [5]. ‘Ligand-gated ion channels’ allow ions to flow across the pore in response to the binding of a chemical messenger (ligand) to the cytoplasmic or extracellular side of the channel [6] These two families are the most important ones, with 100 proteins each in human. IUPHAR, the International Union of basic and clinical PHARmacology (http://www.guidetopharma cology.org/) focuses on pharmacological targets and drugs acting on these targets It captures ion channel features including some functional and biophysical characteristics, as well as several clinically relevant mutations [16]. The goal is to provide a standardized and open ontology that enables the description of voltage-gated ion channel molecular function and the phenotypic effects of ion channel variants

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