Animal Toxins as Comprehensive Pharmacological Tools to Identify Diverse Ion Channels

Ion channels, the principal parties in cell communication, play key roles in the regulation of fundamental physiological processes in different organs and tissues. Consequently they are currently the second largest group of drug targets for existing human therapeutics. Structurally and functionally, ion channels comprise a great diversity of ion-conducting membrane proteins, which in general can be divided into two main but non-exclusive classes: voltage-gated and ligand-gated channels. These are again classified into subfamilies, types and subtypes according to their permeable ion selectivity (e.g., Na + , K + ), gating modulation (e.g., voltage, H + ), and structural properties. Although each type and subtype performs distinct physiological roles, they often possess very similar properties, and their identification and distinction therefore represents a challenging task. A great help in solving this problem was provided by natural compounds that interact selectively with certain types and subtypes of ion channels. A considerable part of such compounds are toxins isolated from animal venoms. Venomous animals have on numerous occasions evolved to chemically overpower their adversaries by modulating their ion channels. However, due to the abundance and diversity of ion channels, the potency of the toxins that perform these tasks is in many ways dependent on their selectivity, and they have therefore evolved to often differentiate between even closely related ion channels in order to more efficiently perform their ecological function.

The progress in investigation is more evident for those ion channels for which selective toxins are available. Perhaps the best examples are nicotinic acetylcholine receptors and voltage-gated calcium, potassium and sodium channels. However, the constantly increasing number of newly identified ion channels requires adequate tools for their studies, a demand that can only partially be met with existing molecular tools. Fortunately, animal venoms remain an under-utilized source of such compounds. Recent developments in analytical techniques has resulted in a dramatic increase in the identification and isolation of new toxins with novel structural folds and features, which may serve as comprehensive tools for ion channel research.

In the Research Topic “Animal toxins as comprehensive pharmacological tools to identify diverse ion channels” we would like to compile an up-to- date collection of the latest developments and improvements related to the use of animal toxins in investigation of different aspects of ion channels. The submissions of original research articles, state-of- the-art review papers, viewpoints and comments on this topic are welcomed. All papers will undergo a peer-review process according to the guidelines of Frontiers in Pharmacology.