Group Abriel

Research Focus:

The main focus of the Abriel laboratory is to investigate mechanisms underlying human diseases caused by dysfunction of ion channels, so-called channelopathies. In particular, one of the main objectives is to elucidate novel molecular and cellular mechanisms of cardiac arrhythmias causing sudden death. To this end, on the one hand, our group investigates ion channel mutations found in patients and families presenting with genetic forms of lethal arrhythmias such as the congenital long QT syndrome, Brugada syndrome, and cardiac conduction disturbances. On the other hand, we are studying new types of regulation of cardiac ion channels relevant to arrhythmogenic mechanisms. The group is currently investigating the regulation of the cardiac sodium channel Nav1.5 and its regulation by interacting proteins (funded by the Swiss National Science Foundation). Another focus is the TRP channel TRPM4 that has shown to be mutated in patients with cardiac conduction disorders. We are focusing on investigating the consequences of these mutations, as well as developing new small molecule modulators of TRPM4 in the framework of the NCCR TransCure (also funded by the Swiss National Science Foundation).

Schematic presentation
Fig. 1 Schematic presentation of the cardiac action potential and the three main ion channels that we are currently studying in the laboratory. The channel Nav1.5 mediates the rapid depolarization of the membrane, whereas the hERG and KCNQ1 channels are involved in the repolarization of the cardiac cell.

Keywords:

sodium channel, potassium channel, hERG channel, TRPM4 channel, cardiac electrophysiology, congenital long QT syndrome, Brugada syndrome, cardiac conduction defects


Original Articles

Gillet L, Rougier JS, Shy D, Sonntag S, Mougenot N, Essers M, Shmerling D, Balse E, Hatem SN, & Abriel H (2015). Cardiac-specific ablation of synapse-associated protein SAP97 in mice decreases potassium currents but not sodium current. Heart Rhythm 12, 181-192.

Ossola D, Amarouch MY, Behr P, Voros J, Abriel H, & Zambelli T (2015). Force-controlled patch clamp of beating cardiac cells. Nano Lett 15, 1743-1750.

Shy D, Gillet L, Ogrodnik J, Albesa M, Verkerk AO, Wolswinkel R, Rougier JS, Barc J, Essers MC, Syam N, Marsman RF, van Mil AM, Rotman S, Redon R, Bezzina CR, Remme CA, & Abriel H (2014). PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function. Circulation 130, 147-160.

Amarouch MY, Kasimova MA, Tarek M, & Abriel H (2014). Functional interaction between S1 and S4 segments in voltage-gated sodium channels revealed by human channelopathies. Channels (Austin) 8, 414-420.

Swan H, Amarouch MY, Leinonen J, Marjamaa A, Kucera JP, Laitinen-Forsblom PJ, Lahtinen AM, Palotie A, Kontula K, Toivonen L, Abriel H, & Widen E (2014). Gain-of-function mutation of the SCN5A gene causes exercise-induced polymorphic ventricular arrhythmias. Circ Cardiovasc Genet 7, 771-781.

Laedermann CJ, Cachemaille M, Kirschmann G, Pertin M, Gosselin RD, Chang I, Albesa M, Towne C, Schneider BL, Kellenberger S, Abriel H, & Decosterd I (2013). Dysregulation of voltage-gated sodium channels by ubiquitin ligase NEDD4-2 in neuropathic pain. J Clin Invest 123, 3002-3013.

Petitprez S, Zmoos AF, Ogrodnik J, Balse E, Raad N, El-Haou S, Albesa M, Bittihn P, Luther S, Lehnart SE, Hatem SN, Coulombe A, & Abriel H (2011). SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circ Res 108, 294-304.

Review Articles

Abriel H, Rougier JS, & Jalife J (2015). Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death. Circ Res 116, 1971-1988.

Marionneau C & Abriel H (2015). Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications. J Mol Cell Cardiol 82, 36-47.

Baruteau AE, Probst V, & Abriel H (2015). Inherited progressive cardiac conduction disorders. Curr Opin Cardiol 30, 33-39.

Laedermann CJ, Decosterd I, & Abriel H (2014). Ubiquitylation of voltage-gated sodium channels. Handb Exp Pharmacol 221, 231-250.

Abriel H & Zaklyazminskaya EV (2013). Cardiac channelopathies: genetic and molecular mechanisms. Gene 517, 1-11.