// SIMONE PELIZZARI 
Flucher Research Group
Institute of Physiology,
Medical University of Innsbruck
// INFORMATION
Nationality: Italian
Education: MSc in Neurobiology at the University of Pavia (Italy)
E-Mail: simone.pelizzari@i-med.ac.at
ORCID
Supervisor: Univ.-Prof. Dr. Bernhard Flucher
// PROJECT
Cav1.1, also known as dihydropyridine receptor (DHPR), is the skeletal muscle calcium channel and voltage-sensor for excitation-contraction (EC) coupling. Its pore-forming subunit (α1s) is folded in four homologous but non-identical repeats, each forming a separate voltage sensing domain (VSD) (helices S1-S4) and part of the channel pore (helices S5-S6). The S4 helices contain regularly spaced positive gating charges, which respond to the changes in membrane potential. Their outward movement upon depolarization critically depends on interactions of their gating charges with negative counter charges in the surrounding helices. Consequently, these ionic interactions control the kinetics and voltage-sensitivity of the L-type calcium currents. Accumulating evidence identifies the VSD I as primary determinant of the slow activation kinetics and VSD IV of the characteristic voltage sensitivity of CaV1.1, while VSDs II and III and their connecting loop have been implicated in activation of EC coupling. We combine structure modeling with site-directed mutagenesis and electrophysiology to investigate the role of CaV1.1 VSDs II and III in channel gating and EC coupling.
Methods: skeletal muscle cell culture and transfection, whole-cell patch-clamp, fluorescent calcium recording.
// INTERNAL COLLABORATIONS