Breakfast Club Seminar Series

Event Details
Contact

Colly Mitchell

Summaries

Summary Sentence: "Regulation of Ryanodine Receptor Calcium Release Channels by Endogenous Effectors" - Ed Balog, PhD - Associate Professor, School of Applied Physiology

Full Summary: The IBB Breakfast Club seminar series was started with the spirit of the Institute's interdisciplinary mission in mind and started to feature local IBB faculty member's research in a seminar format. Faculty are often asked to speak at other universities and conferences, but rarely present at their home institution, this seminar series is an attempt to close that gap. The IBB Breakfast Club is open to anyone in the bio-community.

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"Regulation of Ryanodine Receptor Calcium Release Channels by Endogenous Effectors"

Ed Balog, PhD

Associate Professor
School of Applied Physiology
Georgia Tech

Fluctuations in the intracellular calcium (Ca2+) concentration are used to signal numerous cellular events. Impaired cellular Ca2+ regulation can lead to pathology and cell death, thus tight control of intracellular Ca2+ concentration is vital to the survival of all cells. This a particular challenge for cardiac and skeletal muscle cells as they use the controlled release of Ca2+ from the sarcoplasmic reticulum (SR) to initiate skeletal muscle contraction and the heartbeat. Ryanodine receptor (RyR) Ca2+ channels are the efflux pathway for the release of Ca2+ from the SR, however, these channels are not simple conduits for calcium efflux; rather they integrate cellular signals to finely tune Ca2+ release from intracellular stores. The critical role these channels play in muscle function is exemplified by the mutations in the channels that can lead to lethal cardiac arrhythmia or adverse reactions to anesthetics. Further these channel may contribute to muscle weakness associated with skeletal muscle fatigue and aging. A thorough understanding of RyR channel regulation by endogenous effectors is not only critical for our understanding of muscle function but may contribute to the development of therapeutic agents targeting these channels. I will discuss our work on two potential endogenous channel regulators, S-adenosyl-l-methionine (SAM) and calmodulin (CaM) and briefly describe some of our aging work. Physiological concentrations of SAM, the primary methyl group donor for enzyme-mediated methylation, activated the cardiac isoform of the RyR. This effect of SAM was unrelated to its role as a methyl group donor but rather was mediated by a RyR adenine nucleotide-binding site.  Interestingly, SAM but not ATP activation was associated with a marked increase in the frequency of channel openings to a sub-conductance level. CaM is a small, ubiquitous protein that contains Ca2+-binding sites in each of its two lobes. Ca2+-free CaM activates the skeletal muscle RyR and Ca2+-bound CaM inhibits the channel. We have identified a CaM Ca2+-binding site required for the conversion of CaM from a RyR activator to a channel inhibitor. By manipulating the Ca2+ affinity of this site, we were able to modify the RyR activation profile. Future goals include defining the molecular characteristics required for adenine nucleotide activation of RyR channels and determining the role of CaM in voltage-activation of skeletal muscle.

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Additional Information

In Campus Calendar
Yes
Groups

Parker H. Petit Institute for Bioengineering and Bioscience (IBB)

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Categories
Seminar/Lecture/Colloquium
Keywords
BK Club, IBB
Status
  • Created By: Colly Mitchell
  • Workflow Status: Published
  • Created On: Apr 9, 2013 - 9:10am
  • Last Updated: Oct 7, 2016 - 10:03pm