Clinical Pharmacy Research

144 College Street
Toronto ON M5S 3M2

My work is directed at developing a biophysical understanding of how cellular signals carried by neurotransmitters, cell membrane potential and intracellular second messengers modulate trans-membrane ion channels in neurons and glia cells. The long term goal of this work is to understand how different modulatory mechanisms act in synchrony with one another to produce changes in cellular behaviour. Neuronal function is coordinated to a large extent by ion currents which therefore are targets of regulation. Recent advances in molecular biology have made it possible to delineate the structure of ion channels and of the proteins involved in their regulation, and to hypothesize about the way those structures interact to achieve signal modulation. Parallel advances in methods of cell preparation, and recording ion currents have made it possible to resolve the kinetic properties of ion channels with unprecedented accuracy. Other advances in microscopy and fluorometry have made it possible to monitor the consequences of ion fluxes by ion sensitive dyes and to determine the distribution of ion channels using fluorescently labelled probes. A combination of these approaches are used in my research to investigate biophysical models of ion channel regulation and function and to explain how modulation of channel function changes cell behaviour. Currently my research is focused on:

1. The factors that interact to shape intracellular calcium signals responsible for action potential after-hyperpolarizations and other calcium dependent and initiated events;

2. The factors (including calcium) that control the shape and release probability of synaptic potentials generated between CNS neurons;

3. Mechanisms of stoke induced trauma in neurons and astrocytes;

4. Mechanism of gating of inward rectifier K channels;

5. Computer modelling of ionic signalling;

6. Helpful and harmful actions of free radicals on brain cells.