Brain channelopathies: target validation and novel therapeutic strategies

Project Overview

The entry of calcium ions into cells is mediated by a class of protein (called calcium  channels) that responds to electrical signals by opening of a calcium-selective pore.  Calcium channels are involved in a large number of physiological processes including  muscle contraction, hormone secretion and nerve cell communication in the nervous system. These physiological processes each require optimal amounts of calcium and alteration of the precise amounts can be highly detrimental. In this proposal we will study brain disorders that result from small genetic alterations in calcium channel genes expressed in the nervous system. One of these alterations causes a severe form of migraine headache, another underlies a common type of epilepsy and a third results in a multi-system disorder that includes autism. Further, we will examine a particular calcium channel genetic change that is found in population studies to be strongly correlated with schizophrenia and bipolar disorders. While drugs have been developed to regulate a certain type of calcium channel in the  cardiovascular system and are widely used to treat hypertension and heart failure, as yet there have not been specific treatments developed to target calcium channels involved in diseases of the nervous system. To both address this important therapeutic issue and to help determine how the different genetic alterations in calcium channel genes affect brain functioning, we will test a number of newly developed technical strategies aimed at regulating calcium channel activity. The research team has expertise across a broad area of the neurosciences and together with utilizing animal models of the calcium channel disorders, we aim to provide new insights into how particular genetic alterations affect calcium channel properties resulting in the disruption of normal brain functions and causing serious diseases of the nervous system.

Partners and Donors

Genome BC

Michael Smith Foundation For Health Research

University of Saskatchewan

University of British Columbia