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Ligand recognition and regulation of ion channel proteins

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Ion channel proteins are subject to a rich tapestry of control mechanisms by small molecules and proteins. In physiological settings, these mechanisms link ion channel function with cellular metabolism and signaling pathways, and reflect the diversity of cellular processes regulated by changes in membrane ...

Ion channel proteins are subject to a rich tapestry of control mechanisms by small molecules and proteins. In physiological settings, these mechanisms link ion channel function with cellular metabolism and signaling pathways, and reflect the diversity of cellular processes regulated by changes in membrane voltage. From a pharmacological perspective, elucidation of ion channel control mechanisms has contributed to our understanding of therapeutic mechanisms of action, unsafe drug effects, and improved target-based development of new drugs. Emerging insights into ion channel structures has enabled detailed localization and characterization of blocker and ligand binding sites, and structural motifs and mechanisms that translate binding into changes in channel function. A general rationale for ion channel research is that by developing a deep understanding of the molecular details of ion channel function, we will be poised to develop novel and highly specific modulators and therapeutics. With this frontiers research topic, we hope to address how specific our understanding of ligand or blocker interactions with ion channels has become, and what challenges lie waiting in the 'post-structural' era of ion channel research.

We aim to assemble articles related to recent advances describing molecular details of binding sites for essential ion channel blockers and ligands such as (but not restricted to) lipids, neurotransmitters, nucleotides, polyamines, alcohol, Gβγ subunits, and auxiliary ion channel subunits. Specificity is our goal - we hope to solicit contributions describing progress towards understanding the underpinnings of specific ligand interactions with one ion channel type over another. In addition, we welcome reviews and experimental papers describing coupling mechanisms that link ligand binding to channel functional output, normally by controlling opening and closing of a channel gate.


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