Larry V Hryshko, Professor
Our laboratory investigates a family of ion transport proteins called sodium-calcium exchangers. These proteins play a critical role in controlling the force of cardiac contractions and their malfunction is associated with several distinct cardiac pathologies. We employ electrophysiological, molecular biological and various biophysical techniques to investigate the structure-function relationships of these proteins in molecular detail. We are also devising novel means of modifying their function and examining novel pharmacological agents that target this family of ion transporters.
B.Sc. (Chemistry), Univ. of Winnipeg, 1983
Ph.D. (Pharmacology), Univ. of Manitoba, 1987
Postdoctoral Fellows, Univ. California, Riverside, 1987-91
Assistant Research Physiologist, Univ. of California 1991-94
Assistant Professor (Physiology), University of Manitoba 1994-present
Associate Professor (Physiology), University of Manitoba
Professor (Physiology), University of Manitoba
Academic Achievements
Research Interests
My research focuses on understanding how intracellular calcium levels are controlled in cardiac muscle as this directly controls the strength of cardiac contractions. Calcium homeostasis is regulated by several distinct mechanisms in cardiac cells. The operation and modulation of individual calcium transport proteins are under investigation. The object is to understand the function of the individual components as they pertain to integrated cardiac function. Projects of current interest include:
- Cardiac excitation-contraction coupling: Cardiac cells are electrically excitable. For each individual contraction, an initial electrical event is translated into a subsequent mechanical event. The coupling of these events and potential means of modulating this relationship are being investigated using electrophysiological and mechanical techniques.
- Cardiac sodium-calcium exchange: Sodium-calcium exchange is a major mechanism for removing intracellular calcium to enable cardiac relaxation. Patch clamp techniques are being used to study transport properties and regulatory mechanisms in the native sodium-calcium exchanger in sarcolemma and the cloned sodium-calcium exchanger expression Xenopus oocytes.
- Cardiac calcium channels: Physiological and pharmacological modulation of cardiac calcium channels is being studied at the whole cell and single channel level using patch clamp techniques.
- Cardiac sarcoplasmic reticulum: The sarcoplasmic reticulum is being studied by examination of the force-interval relationship and rapid cooling contracture techniques.
- Pathological alterations in cardiac excitation-contraction coupling: The basic research described above is designed to gain an integrated overview of cardiac function under physiological conditions so that alterations occurring during various pathophysiology are under investigation including ischemia-reperfusion injury, metabolic inhibition, and free radical mediated damage. A major emphasis to determine which systems fail to maintain calcium homeostasis and thus contribute to irreversible myocardial cell injury.
See Also:
St. Boniface Research Ctr
R3032 - 351 Tache Av
Winnipeg MB CANADA
R2H 2A6
Tel: 204 235 3662
Fax: 204 233 6723