© Springer Science+Business Media New York 2015 1
C. Ahern, S. Pless (eds.), Novel Chemical Tools to Study Ion Channel Biology,
Advances in Experimental Medicine and Biology 869,
DOI 10.1007/978-1-4939-2845-3_
S. A. Pless ()
Department of Drug Design and Pharmacology, Center for Biopharmaceuticals,
University of Copenhagen, Copenhagen, Denmark
e-mail: [email protected]
C. A. Ahern
Department of Molecular Physiology and Biophysics, University of Iowa,
Iowa City, IA, 52246, USA
e-mail: [email protected]
Introduction
Applying Chemical Biology to Ion Channels
Stephan A. Pless and Christopher A. Ahern
Abstract Ion channels are membrane-spanning proteins that control the flow of
ions across biological membranes through an aqueous pathway. The opening or
closing of this pore can be controlled by a myriad of physiological inputs (voltage,
ligands, temperature, metabolites, pH), which in turn allow for the controlled flux
of ions across membranes, resulting in the generation of minute electrical signals.
The functional implications of ion channel function on physiological processes
are vast. Electrical impulses, in the form of action potentials or diverse chemo-
electrical signals, coordinate the syncytium of the heart beat, support a myriad of
neuronal communication pathways, insulin secretion, and are central to the immune
response, with more roles being discovered virtually everyday. Thus, ion channel
function is a biophysical process that is central to biological life at many levels. And
with over 500 channel-forming subunits known today in humans, this large class of
proteins is also increasingly recognised as important drug targets, as inherited or
acquired ion channel dysfunction are known causes of disease.
Keywords Ion channels · Chemical biology · Side chain protonation · Cysteine
modifications · Unnatural amino acids
Ion channels are membrane-spanning proteins that control the flow of ions across
biological membranes through an aqueous pathway. The opening or closing of this
pore can be controlled by a myriad of physiological inputs (voltage, ligands, tem-
perature, metabolites, pH)), which in turn allow for the controlled flux of ions across
membranes, resulting in the generation of minute electrical signals. The functional