About this Research Topic

Background

Ion channels and transporters play crucial roles in maintaining cellular homeostasis and regulating various physiological processes. To fully understand the physiological roles of specific ion channels and transporters and their dysfunctions in disease states, the complex interplay between protein structure and function must be understood in the native setting. New research methodologies offer novel insights into ion channel and transporter structure and function. In addition to providing greater mechanistic detail, these methodologies provide physiological context and facilitate the identification of new drug binding sites.

Over the last decade, single-molecule imaging of integral membrane proteins in re-constructed lipid bilayers has experienced a ‘resolution revolution’. Recently, novel methodologies have been developed to correlate this structural data with functional information, facilitating a better understanding of ion channel and transporter function and their modulation by drugs.

The study of ion channels has been revolutionized by chip-based electrophysiology. The latest automated patch clamp systems enable even higher throughput analysis for screening large functional compound libraries. These systems can be used to analyze the biophysical properties of a wide range of ion channels, and to provide some important physiological context. Moreover, protocols for analyzing ion channels in native cells and induced pluripotent stem cells have been developed. High throughput systems for automated measurements of electrogenic transporter activities are also available.

Another fast-developing approach involves the development of subtype and conformation specific antibodies to investigate the expression and function of specific ion channels and transporters. The subtype specific antibodies enable the integration of cell sorting technology into excitable cell physiology, facilitating precise characterization of ion channel subtypes in isolated cells and a better understanding of their functions. The conformation specific antibodies may activate or inhibit the functions of ion channels and transporters, potentially providing a therapeutic effect. In recognition of these developments, there is a growing trend to target these important membrane proteins with biologics.

Finally, the development of organ or tissue-based 3D systems and the application of transgenic approaches have increased our understanding of the role of ion channels and transporters in disease states. These new models provide a physiologically relevant environment to investigate the underlying mechanisms and elucidate potential therapeutic interventions.

The goal of this Research Topic is to explore and highlight several emerging approaches that have transformed the study of ion channels and transporters, delving into the latest advancements and techniques that offer a deeper understanding of these important membrane proteins and their roles as therapeutic targets in various pathologies.

Topics include but are not limited to:

- Use of structural data from single-molecule imaging to elucidate functional transitions in ion channel and transporter proteins and to direct drug design.
- Use of chip-based high throughput systems to identify modulators of ion channel and transporter function in native cells.
- Use of antibodies to investigate and modulate ion channel and transporter structure and function.
- Cell sorting technology integrated into excitable cell physiology.
- Use of organ or tissue-based 3D systems to study ion channels and transporter proteins.
- Transgenic approaches to studying ion channels and transporters in disease.

Keywords: ion channels, channelopathies, chip-based ion channels, structural data, transporters, membrane proteins, single-molecule imaging, cell sorting, antibodies, electrophysiology, drug design

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