From Cardiac arrhythmia to epilepsy - Ion channels in health and disease

Our lab studies the structure and function of ion channels, membrane protein responsible for electrical signaling in excitable cells. Ion channel genes are targeted by hundreds of genetic variants that result in 'channelopathies', a set of severe disorders ranging from inherited cardiac arrhythmias to chronic pain and congenital epilepsy.


We use a combination of structural biology and electrophysiology.


Latest paper: Das S, Gilchrist J, Bosmans F*, Van Petegem F* (2016)

Binary architecture of the Nav1.2-β2 signaling complex. eLife e10960





The pore-forming α-subunit of sodium channels can associate with multiple protein building blocks, one of which is called the β2 subunit. Until now, it was not known exactly how these two partners come together to form a channel complex. We. have now visualized the 3D structure of the β2 subunit in very high detail by using X-ray crystallography. The level of detail in the structure allowed the identification of amino acids that make up the region that anchors to the sodium channel. By making use of tarantula toxin and mutagenesis, we have been able to identity the exact anchoring point between the α- and β-subunits.Cys at position 55 in the β2 subunit forms a disulfide bond with Cys at position 910 in the sodium channel domain II pore loop, thereby suggesting a 1:1 stoichiometry.


This work was performed in collaboration with the lab of Frank Bosmans (Johns Hopkins University)



keywords: cardiac arrhythmia, epilepsy, ion channel, CPVT, Dravet syndrome, malignant hyperthermia, central core disease, excitation-contraction coupling, ryanodine receptor, sodium channel, calcium channel, voltage-gated sodium channel, calmodulin, X-ray crystallography, ryanodine, RyR, RyR1, RyR2, RyR3, high resolution, structure, arrhythmia, genetic disorder, ITC, isothermal titration calorimetry, Brugada syndrome, Long QT syndrome, arrhythmia, channel, electrophysiology, GEFS+, Vancouver, UBC, Biochemistry, Canada
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Van Petegem Lab © 2007, updated: Feb 22/ 2016