Extracellular Ion Channel Inhibitor Antibodies

Abstract

For many ion channels there are no specific pharmacological agents and this impedes searches for the physiological and pathological functions of the ion channels in native systems and restricts opportunity for therapeutic drug development. Antibodies can display high specificity for their target proteins and are routinely engineered to recognise proteins in many experimental procedures and increasingly as therapeutic agents. The unlimited diversity and potential for high specificity make antibodies attractive as biological tools and drugs, although they are not without problems. Along with other investigators we have explored targeting of the E3 extracellular loop (or turret) as an approach for the generation of antibodies with the potential to block certain types of ion channel with isoform specificity. The approach has led to success with nine ion channels and effective use in vitro and in vivo. Here we review current knowledge and experience of channel-blocking antibodies, focusing particularly but not exclusively on E3-targeting.