Role of cannabinoids on fast-inactivation of cardiac Nav channels

Cannabinoids are natural products derived from the Cannabis sativa plant (commonly known as marijuana). Cannabidiol (CBD), the main non-psychotropic cannabinoid is reputed to have medicinal benefits and is approved for the treatment of two seizure disorders. Other non-psychotropic cannabinoids, like cannabinol and cannabigerol, are less studied. We previously found that CBD both directly and indirectly affects voltage-gated sodium channel (Nav) function. The direct effects of CBD on Nav involve sodium current reduction, which we suggest is caused by a physical block of the channel; the mechanism of this block remains unknown. We now seek to gain more detailed knowledge of how CBD and other cannabinoids directly affect the biophysical properties of the cardiac Nav channel (Nav1.5) by measuring Nav1.5 gating charge movements. Notably, CBD reduces seizure activity associated with Dravet Syndrome, an inherited seizure disorder caused by mutations in neuronal Nav channels. Therefore, we aim to further determine if cannabinoids could be used to reduce proarrhythmic activity associated with long-QT 3 (LQT3), an inherited heart disease caused by mutations in Nav1.5.

Faculty Supervisor:

Peter Ruben

Student:

Dana Alannis Page

Partner:

Akseera Pharma Corp

Discipline:

Kinesiology

Sector:

University:

Simon Fraser University

Program: