//     MARTIN HEISS

Flucher Research Group
Institute of Physiology
Medical University of Innsbruck

//     INFORMATION

Nationality: Austria
Education: MSc in Chemistry at the Leopold-Franzens-University in Innsbruck
E-Mail: martin.heiss@i-med.ac.at
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Supervisor: Univ.-Prof. Dr. Bernhard E. Flucher

 

//     PROJECT

Voltage-gated calcium channels regulate key functions in neuron and muscle cells.
CaV1.1 is an L-type voltage-dependent calcium channel that is found in skeletal muscle cells.
Its main function is to sense voltage changes upon membrane depolarisation which plays a crucial role in the process of excitation-contracting coupling (EC) and furthermore in the contraction of a muscle. The pore-forming subunit () contains four homologous repeats. Each repeat consists of six (S1-S6) transmembrane helices and can be divided into two functional domains, the voltage-sensing domain (S1-S4) and the pore-forming domain (S5-S6). The S4 helix in the voltage-sensing domain contains regularly spaced positively charged residues which respond to changes in membrane potential. Thus, depolarisation of the membrane represents a driving force that results in an outward movement of the S4 segment. These movements are directly coupled to conformational changes that are responsible for pore opening. This outward movement strongly depends on ionic interactions with the surrounding negatively charged residues. By combining theoretical (homology modelling, molecular dynamic simulations) and electrophysiological (whole-cell patch-clamping, site-directed mutagenesis) methods we try to biophysically characterize key determinants to structurally and functionally understand the voltage-gating mechanism of individual voltage-sensing domains, but also of the whole .

Methods: whole-cell patch-clamp, skeletal muscle cell culture and transfection, site-directed mutagenesis, homology modelling, molecular dynamic simulations, enhanced sampling techniques

//     INTERNAL COLLABORATIONS

Marta Campiglio
Petronel Tuluc

//     EXTERNAL COLLABORATIONS

Univ.-Prof. DDr. Klaus R. Liedl and Dr. Monica L. Fernández-Quintero at the Institute of Theoretical Chemistry of the Leopold-Franzens University Innsbruck