Antibodies to Ion Channels

Ion channels are integral membrane proteins forming pores that allow passage of ions such as sodium, potassium, calcium, chloride, and others to traverse the hydrophopic environment of a cell's lipid bilayer membrane. Ion channels can be constitutively open, or more importantly, they can be voltage-gated or ligand gated. Voltage-gated channels open when the potential across the membrane rises above or falls below a specific threshold, while ligand-gated channels open (or close) upon binding of a ligand. Another important type of ion channels are metabotropic ion channels, which are gated by G-protein subunits or intracellular second messengers. Ion channels are among the most important proteins in biology, they are essential to neural conduction, synaptic transmission, osmosis, respiration, and many other biological processes. Impaired ion channel function can cause disease such as cystic fibrosis, in which the gene encoding a chloride channel known as CFTR carries loss of function mutations. Other ion channels have been targeted for inhibitor discovery in a variety of disease indications, and drugs targeting ion channels already generate multi-billion dollars in sales per annum.

Ion channels are usually not available as purified antigens for immunization. Rather, antibodies against ion channels are being developed by immunization with whole cells or cell membranes that express or over-express the ion channel of interest. Alternatively, immunization can be carried out with peptides, fragments, or recombinant structural domains derived from ther channel of interest. Antibodies against ion channels can be evaluated further by a technology known as patch-clamp, that can measure currents through single ion channel molecules. In patch-clamp experiments, neutralizing antibodies manifest themselves by blocking the ion flux through the channel of interest following activation with applicable ligand.

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