KV1.5 and Kv4.3 Potassium channels modulation

Despite the progress in the knowledge of the human interactome and its relationship with disease, multiple protein-protein interactions remain to be deciphered. The knowledge of a protein interactome is essential for its validation as therapeutic target and for the discovery of drug candidates. Specific modulators and biosensors of protein activity are key and complementary tools for this purpose, and constitute one objective of our research.

Ion channels form signaling complexes or channelosomes, which are essential for an optimal, fast and efficient transmission of signals, either from the extracellular or from the intracellular media. The knowledge of the composition of these channelosomes is, therefore, essential for the validation of proteins as new therapeutic targets and for the discovery of useful drug candidates.

In the human myocardium, Kv1.5 and Kv4.3 channels generate the ultrarapid and the transient outward potassium currents (IKur and Ito, respectively), which are the main responsible of the human atrial repolarization.

The aim of this Project is the search of new modulators and fluorescence biosensors for the study of protein interactions within the Kv1.5 and Kv4.3 channelosomes as a source of new drugs for the treatment of atrial fibrillation (AF), the most common arrhythmia. We focused on the interactions between the potassium channel interacting protein 2 (KChIP2), Lgi3-4 and Sig1R with the Kv1.5 and Kv4.3 channels.

Using a multidisciplinary approach, which involved molecular design, organic synthesis, biophysics, electrophysiology and cellular biology we will help to identify new potential pharmacological targets, as well as new chemical entities potentially useful in the development of new valuable drugs for the treatment of atrial fibrillation.

Coordinated project with Dra. Carmen Valenzuela IIBM “Alberto-Sols”

Finantial supporting: Ministerio de Ciencia e Innovación PID2019-104366RB-C22 and  Fondo Social Europeo