Dr. Peter Ruben

B.A. George Washington University
M.S. George Washington University
Ph.D. University of Calgary

Postdoctoral: Hopkins Marine Station, Stanford University

 Professor, Department of Biomedical Physiology and Kinesiology, SFU
Associate Member of the Department of Molecular Biology and Biochemistry, SFU
Associate Member of the Department of Biological Sciences, SFU
Associate Member of the Department of Cell and Physiological Science, UBC
Molecular Cardiac Physiology Group

Research Interests:

The long-term goals of our research are to assess the biophysical sequelae of identifiable sodium channel mutations and substitutions that lead to changes in cellular excitability and toxin resistance.

The sodium channel is a crucial component in electrically excitable cells throughout the animal kingdom and constitutes the primary basis on which electrical impulses are founded in nerve and muscle cells. Its function requires an exquisite balance between its various gating properties as well as its ion selectivity. These properties are based on a sequence of amino acids that imparts voltage-sensitive mobility and sodium ion selectivity to the molecule's ornate structure. Both the complexity and importance of the sodium channel has made it an ideal target for toxins, medicinal and recreational drugs, and the molecular basis of heritable neurological, muscular, and cardiovascular disease states. Using a unification of molecular and biophysical approaches, our research leads to a more complete understanding of the structure-function relationships within the sodium channel molecule. In so doing, we relate channel availability to a variety of disease states including idiopathic ventricular fibrillation, epilepsy, nondystrophic myotonia, and periodic paralysis, and the pharmacological alleviation of these conditions.

The general aims of our research are to explore the biophysical properties of sodium channels that regulate their availability. We have discovered that sodium channel availability, and thus cell excitability, is most heavily dependent on steady-state inactivation, a phenomenological process that is comprised of the physical states of fast and slow inactivation. Although fast inactivation has been well defined, slow inactivation is still an elusive process and thus forms a primary target of my laboratory's work. Recently, we have discovered that defects in deactivation are a consistent theme underlying non-dystrophic myotonia.

The specific experimental aims of our research are:

  1. to explore the molecular determinants and biophysical underpinnings of diseases of excitability in cardiac muscle, skeletal muscle, and neurons;
  2. to use toxin resistance in sodium channels as a marker for adaptation and parallel evolution;
  3. to determine the interactions between activation, deactivation, fast inactivation and slow inactivation in the regulation of sodium channel availability and the contribution of sodium channels to cell excitability, the responsiveness of cells to excitatory synaptic input, and the production of action potentials.

In pursuit of these goals, we use PCR-based site-directed mutagenesis, heterologous expression in Xenopus oocytes and HEK293 cells, patch clamp electrophysiology to measure ionic currents, cut-open oocyte electrophysiology to measure ionic and gating currents, and site-directed fluorescence labeling to measure molecular movements.

Recent Publications: