Cation channel TRPM4

The calcium-activated cationic channel TRPM4 (transient receptor potential melastatin 4) is predominantly expressed in cells of the cardiovascular, nervous and immune system, pancreas and kidney. TRPM4 is involved in many calcium-dependent cellular processes, such as control of excitable cell activity, insulin secretion or mast cells degranulation. Several genetic variants in the human gene of TRPM4 were linked to conduction disorders leading to cardiac arrhythmias in patients. Furthermore, TRPM4 has been recently linked to the pathogenesis of multiple sclerosis. The focus of the project is on cardiac arrhythmias and multiple sclerosis, as well as development of more potent and selective small molecule modulators. Using biochemical and electrophysiological approaches, the characterization of mutations linked to conduction disorders is pursued. In vivo, the role of TRPM4 in cardiac arrhythmias and multiple sclerosis is assessed using knock-out/in mouse models and a multiple sclerosis mouse model, respectively, in combination with TRPM4 small molecule modulators.