IMR Press / FBL / Volume 23 / Issue 1 / DOI: 10.2741/4581

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Differences in ion channel phenotype and function between humans and animal models

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1 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston TX 77030, USA
2 Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston TX 77030, USA
3 Center for Drug Discovery and Biology of Inflammation Center, Baylor College of Medicine, Houston TX 77030, USA
Front. Biosci. (Landmark Ed) 2018, 23(1), 43–64; https://doi.org/10.2741/4581
Published: 1 January 2018
(This article belongs to the Special Issue Electrophysiology from bench to bedside)
Abstract

Ion channels play crucial roles in regulating a broad range of physiological processes. They form a very large family of transmembrane proteins. Their diversity results from not only a large number of different genes encoding for ion channel subunits but also the ability of subunits to assemble into homo- or heteromultimers, the existence of splice variants, and the expression of different regulatory subunits. These characteristics and the existence of very selective modulators make ion channels very attractive targets for therapy in a wide variety of pathologies. Some ion channels are already being targeted in the clinic while many more are being evaluated as novel drug targets in both clinical and preclinical studies. Advancing ion channel modulators from the bench to the clinic requires their assessment for safety and efficacy in animal models. While extrapolating results from one species to another is tempting, doing such without careful evaluation of the ion channels in different species presents a risk as the translation is not always straightforward. Here, we discuss differences between species in terms of ion channels expressed in selected tissues, differing roles of ion channels in some cell types, variable response to pharmacological agents, and human channelopathies that cannot fully be replicated in animal models.

Keywords
Ion channels
Disease
Drug Development
Animal Model
Target Validation
Pharmacology
Review
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