Title: Cardiac and skeletal muscle disorders: high-resolution insights into channelopathies
Speaker: Prof. Filip Van Petegem, Faculty of Medicine, University of British Columbia, Canada
Time: Oct 14th, Monday, 15:00 pm
Venue: Building 24#-C406
Host: Prof. Michael Yuchi
Abstract:
The contraction of cardiac and skeletal muscle is mediated by a temporary rise in cytosolic calcium levels. The process requires a coupling between calcium-selective channels in the plasma membrane (L-type voltage-gated calcium channels) and in the Sarcoplasmic Reticulum (Ryanodine Receptors). Also known as 'excitation-contraction coupling', this process is thought to proceed through functional links in cardiac muscle, and through direct mechanical links between both membrane proteins in skeletal muscle. Here I discuss our lab's efforts to understand the process of muscle excitation-contraction coupling and the many disease mutations that affect the various components, leading to inherited cardiac arrhythmia, myopathies, and malignant hyperthermia. In particular, we have been investigating the role of STAC3, a protein essential in the mechanical coupling. We find it to associate with the calcium channels via multiple sites that each have distinct functional effects. We also investigate how kinases like PKA associate with the Ryanodine Receptor, showing an interface that goes far beyond a typical consensus site. Mapping mutations on the various components of the excitation-coupling machinery fall into different categories.
