IEEE Winnipeg Section


BME Seminar



Mechanical-Energetic Coupling in Airway Smooth Muscle


Thursday, May 30, 2013 from 5:30-6:30pm


E2-330 EITC, Fort Garry Campus, University of Manitoba


Dr. Gary Sieck
Professor and Chair, Physiology and Biomedical Engineering
Mayo Clinic, rochester, MN


Asthma affects more than 20 million people in the USA (~10% of the population), and more than 300 million people worldwide. The incidence and severity of asthma is increasing, with a 47% increase in associated death rate over the past 10 years. Asthma is characterized by airway smooth muscle (ASM) hyperresponsiveness and remodeling, triggered by inflammation. Changes in excitation-contraction coupling most likely underlie ASM hyperreactivity, possibly as a result of an increased cytosolic Ca2+ ([Ca2+]cyt) response to agonist stimulation. Agonist-induced elevation of [Ca2+]cyt results from a number of underlying mechanisms including: 1) Ca2+ influx through store-operated Ca2+ entry (SOCE) as well as voltage and ligand gated channels; and 2) endoplasmic/sarcoplasmic reticulum (ER/SR) Ca2+ release the through inositol 1,4,5-trisphosphate (IP3) and ryanodine receptor (RyR) channels. The regulation of [Ca2+]cyt in ASM cells is dynamic with spontaneous Ca2+ transients (Ca2+ sparks) and propagating [Ca2+]cyt waves. Within a localized region of an ASM cell, these [Ca2+]cyt waves reoccur reflecting localized [Ca2+]cyt oscillations. Mitochondria lie juxtaposed with the SR and mitochondrial Ca2+ uptake (increased [Ca2+]mito) helps to couple mitochondrial oxidative phosphorylation to the increasing energetic demands of increased force generation. The dynamic nature of [Ca2+]cyt and [Ca2+]mito regulation in ASM cells is also evident by the movement of mitochondria and SR in relation to each other and the fission-fusion state of mitochondria. Each of these steps in the complex regulation of [Ca2+]cyt and [Ca2+]mito regulation in ASM is affected by exposure to inflammatory cytokines (e.g., TNF and IL13) and the associated ER/SR and mitochondrial stress response.

Speaker Bio:

Gary C. Sieck, Ph.D., is the Vernon F. and Earline D. Dale Professor and Chair of the Department of Physiology & Biomedical Engineering at Mayo Clinic. He is also a Mayo Distinguished Investigator and the Director of the Biomedical Engineering Program in the Mayo Graduate School. From 2006-2012, he also served as Dean for Research Academic Affairs at Mayo.

Dr. Sieck received a Ph.D. in Physiology and Biophysics from the University of Nebraska in 1976. He then completed postdoctoral training in Neurophysiology at UCLA in 1979, where he continued as a faculty member in the Department of Anatomy and Cell Biology. In 1987, he moved to the University of Southern California to join the faculty in the Department of Biomedical Engineering. Dr. Sieck moved to Mayo Clinic in 1990.

At Mayo, he has mentored 10 predoctoral students, more than 60 postdoctoral fellows and 20 visiting scientists. He is a recipient of both the Mayo Research Educator Award, the Mayo Graduate School Dean’s Recognition Award.

Dr. Sieck served as President of the American Physiological Society (2009-2011) and President of the Association of Chairs of Departments of Physiology (2010-2012). He is an elected Fellow of the American Institute of Medical and Biological Engineering. In the past, he served as member of the Board of Directors of the American Thoracic Society and on the Council of the American Lung Association. He was editor-in-chief of the Journal of Applied Physiology from 1999-2005, and is currently editor-in-chief of Physiology. He is also a member of several editorial boards and advisory councils. Dr. Sieck has also served on several study sections of the National Institutes of Health (NIH).

Dr. Sieck’s research focuses on neural control of respiratory muscles. In the diaphragm muscle, he has explored neuromuscular plasticity related to spinal cord injury and muscle weakness associated with mechanical ventilation and the intensive care environment. In airway smooth muscle, he has examined abnormalities in intracellular calcium regulation and excitation-coupling associated with asthma and chronic obstructive pulmonary disease. He has published more than 330 peer-reviewed papers and his research has been continuously funded by the NIH for more than 30 years.